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gard | https://rarediseases.info.nih.gov/diseases/10327/24-dienoyl-coa-reductase-deficiency | PL8XPYQ | 2,4-Dienoyl-CoA reductase deficiency | C1857252 | 0 | 2,4-dienoyl-coa reductase deficiency. 2,4-Dienoyl-CoA reductase deficiency is associated with hypotonia and respiratory acidosis in infancy. This condition may be associated with the DECR1 gene and likely has an autosomal recessive pattern of inheritance. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. SummaryClinical description.Primary hyperoxaluria type 3 (PH3) is characterized by recurring calcium oxalate stones beginning in childhood or adolescence and, on occasion, nephrocalcinosis or reduced kidney function. In 50%-65% of individuals with PH3 stone formation begins prior to age five years. Although the frequency and severity of stone activity often seem to abate by adolescence and adulthood, stone formation can occur throughout life and some adults have many stones. To date systemic oxalosis has not been reported in PH3.Diagnosis/testing.The diagnosis of PH3 is established in a proband with calcium oxalate kidney stone(s) and/or nephrocalcinosis, urine oxalate >0.7 mmol/1.73 m2/24 hours (in those with preserved kidney function), increased concentration of plasma oxalate (particularly in those with reduced kidney function), and biallelic (homozygous or compound heterozygous) pathogenic variants in HOGA1. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. To date systemic oxalosis has not been reported in PH3.Diagnosis/testing.The diagnosis of PH3 is established in a proband with calcium oxalate kidney stone(s) and/or nephrocalcinosis, urine oxalate >0.7 mmol/1.73 m2/24 hours (in those with preserved kidney function), increased concentration of plasma oxalate (particularly in those with reduced kidney function), and biallelic (homozygous or compound heterozygous) pathogenic variants in HOGA1.Management.Treatment of manifestations: Reduction of urine supersaturation of calcium oxalate by maintaining high oral fluid intake at all times and use of an inhibitor of calcium oxalate crystallization such as potassium or sodium citrate; prevention of stone complications by prompt relief of urinary tract obstruction and treatment of urinary tract infections; and avoidance of marked dietary oxalate excess.Prevention of primary manifestations: Same as Treatment of manifestations.Surveillance: For those who are stable, annual clinical assessment of: stone- | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. heterozygous) pathogenic variants in HOGA1.Management.Treatment of manifestations: Reduction of urine supersaturation of calcium oxalate by maintaining high oral fluid intake at all times and use of an inhibitor of calcium oxalate crystallization such as potassium or sodium citrate; prevention of stone complications by prompt relief of urinary tract obstruction and treatment of urinary tract infections; and avoidance of marked dietary oxalate excess.Prevention of primary manifestations: Same as Treatment of manifestations.Surveillance: For those who are stable, annual clinical assessment of: stone-related symptoms (pain), frequency of passage of urinary stones and/or gravel, urinary tract infection; adherence to high fluid intake and medication schedule; annual: assessment of kidney function by serum creatinine, measurement of plasma oxalate concentration in those with impaired renal function, 24-hour urine oxalate and supersaturation study, and renal ultrasound examination or other imaging to monitor for stone formation.Agents/circumstances to avoid: Intravascular volume contraction, delays in treatment of acute | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. stable, annual clinical assessment of: stone-related symptoms (pain), frequency of passage of urinary stones and/or gravel, urinary tract infection; adherence to high fluid intake and medication schedule; annual: assessment of kidney function by serum creatinine, measurement of plasma oxalate concentration in those with impaired renal function, 24-hour urine oxalate and supersaturation study, and renal ultrasound examination or other imaging to monitor for stone formation.Agents/circumstances to avoid: Intravascular volume contraction, delays in treatment of acute stone episodes, marked dietary oxalate excess, high-dose ascorbic acid, and nephrotoxic agents.Evaluation of relatives at risk: Presymptomatic diagnosis and treatment is warranted in relatives at risk to reduce stone formation and the risk of nephrocalcinosis and chronic kidney disease.Pregnancy management: Adequate fluid intake throughout the pregnancy.Genetic counseling.PH3 is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. Intravascular volume contraction, delays in treatment of acute stone episodes, marked dietary oxalate excess, high-dose ascorbic acid, and nephrotoxic agents.Evaluation of relatives at risk: Presymptomatic diagnosis and treatment is warranted in relatives at risk to reduce stone formation and the risk of nephrocalcinosis and chronic kidney disease.Pregnancy management: Adequate fluid intake throughout the pregnancy.Genetic counseling.PH3 is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the HOGA1 pathogenic variants in the family are known.DiagnosisSuggestive FindingsPrimary hyperoxaluria type 3 (PH3) should be considered in any individual with the following:Recurring calcium oxalate stonesOnset of stone | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the HOGA1 pathogenic variants in the family are known.DiagnosisSuggestive FindingsPrimary hyperoxaluria type 3 (PH3) should be considered in any individual with the following:Recurring calcium oxalate stonesOnset of stone disease in childhood or adolescenceNephrocalcinosisReduced kidney function in the presence of calcium stones or nephrocalcinosisFamily history of chronic kidney disease and/or recurring calcium oxalate stones consistent with autosomal recessive inheritanceNote: Since idiopathic stone disease is very common and since calcium oxalate is found in approximately 80% of stones , a high index of clinical suspicion is necessary to identify the small proportion of individuals who form calcium oxalate stones as a result | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. :Recurring calcium oxalate stonesOnset of stone disease in childhood or adolescenceNephrocalcinosisReduced kidney function in the presence of calcium stones or nephrocalcinosisFamily history of chronic kidney disease and/or recurring calcium oxalate stones consistent with autosomal recessive inheritanceNote: Since idiopathic stone disease is very common and since calcium oxalate is found in approximately 80% of stones , a high index of clinical suspicion is necessary to identify the small proportion of individuals who form calcium oxalate stones as a result of PH3.Establishing the DiagnosisAlgorithms for the diagnosis of the primary hyperoxalurias have recently been published (see Figure 1).Figure 1. Algorithm for the diagnostic evaluation of primary hyperoxaluria in an affected individual 1. Chronic kidney disease is defined as a glomerular filtration rate <50 mL/min/1.73 m2, or serum creatinine ≥2x normal for age.The diagnosis of PH3 is established in a | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. individuals who form calcium oxalate stones as a result of PH3.Establishing the DiagnosisAlgorithms for the diagnosis of the primary hyperoxalurias have recently been published (see Figure 1).Figure 1. Algorithm for the diagnostic evaluation of primary hyperoxaluria in an affected individual 1. Chronic kidney disease is defined as a glomerular filtration rate <50 mL/min/1.73 m2, or serum creatinine ≥2x normal for age.The diagnosis of PH3 is established in a proband with the clinical findings of calcium oxalate kidney stone(s) and/or (on occasion) nephrocalcinosis and the following biochemical and molecular genetic findings.Biochemical FindingsUrine oxalate. >0.7 mmol/1.73 m2/24 hours in individuals with preserved kidney function (GFR >40 mL/min/1.7m2)Note: (1) Urine oxalate may be lower in individuals with advanced chronic kidney disease ( | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. The diagnosis of PH3 is established in a proband with the clinical findings of calcium oxalate kidney stone(s) and/or (on occasion) nephrocalcinosis and the following biochemical and molecular genetic findings.Biochemical FindingsUrine oxalate. >0.7 mmol/1.73 m2/24 hours in individuals with preserved kidney function (GFR >40 mL/min/1.7m2)Note: (1) Urine oxalate may be lower in individuals with advanced chronic kidney disease (CKD). (2) In children the oxalate excretion rate must be corrected for 1.73 m2 body surface area (BSA). (3) Urine oxalate should preferably be measured in a 24-hour urine sample; however, when timed urine collections cannot be obtained, a random urine oxalate/creatinine ratio can be used. Since normal ranges for oxalate/creatinine vary during childhood by age, age-related normal values should be consulted for accurate interpretation ( | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. lower in individuals with advanced chronic kidney disease (CKD). (2) In children the oxalate excretion rate must be corrected for 1.73 m2 body surface area (BSA). (3) Urine oxalate should preferably be measured in a 24-hour urine sample; however, when timed urine collections cannot be obtained, a random urine oxalate/creatinine ratio can be used. Since normal ranges for oxalate/creatinine vary during childhood by age, age-related normal values should be consulted for accurate interpretation (see Table 1).Plasma oxalate. >20 µmol/L and/or systemic oxalosis in individuals with chronic kidney disease stages 3b, 4, and 5 (GFR <45 mL/min/1.73m2)Urine glycolate, L-glycerate, 4-hydroxyoxoglutarate (HOG), and dihydroxyglutarate (DHG)Increased urine glycolate in the presence of hyperoxaluria is suggestive, but | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. normal values should be consulted for accurate interpretation (see Table 1).Plasma oxalate. >20 µmol/L and/or systemic oxalosis in individuals with chronic kidney disease stages 3b, 4, and 5 (GFR <45 mL/min/1.73m2)Urine glycolate, L-glycerate, 4-hydroxyoxoglutarate (HOG), and dihydroxyglutarate (DHG)Increased urine glycolate in the presence of hyperoxaluria is suggestive, but not diagnostic of PH1.Increased urine L-glycerate in an individual with hyperoxaluria suggests PH2 (see Differential Diagnosis).Increased HOG and DHG suggest PH3 (see Differential Diagnosis).Note: The patient should not be receiving pyridoxine or vitamin supplements when urine and plasma oxalate and urine glycolate measurements are being obtained for the purpose of diagnosis.Table 1. Random Urine Oxalate-to-Creatinine (Ox/Cr) Ratio | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. presence of hyperoxaluria is suggestive, but not diagnostic of PH1.Increased urine L-glycerate in an individual with hyperoxaluria suggests PH2 (see Differential Diagnosis).Increased HOG and DHG suggest PH3 (see Differential Diagnosis).Note: The patient should not be receiving pyridoxine or vitamin supplements when urine and plasma oxalate and urine glycolate measurements are being obtained for the purpose of diagnosis.Table 1. Random Urine Oxalate-to-Creatinine (Ox/Cr) Ratio by AgeView in own windowAgeUpper Limit of Normal (mmol/mmol) 2(mg/mg)<6 months 10.370.296 months to 2 years0.260.20>2 years to 5 years0.140.116 to 12 years0.080.06Based on: Gibbs & Watts , Barratt et al , Morgenstern et al , von Schnaken | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. to-Creatinine (Ox/Cr) Ratio by AgeView in own windowAgeUpper Limit of Normal (mmol/mmol) 2(mg/mg)<6 months 10.370.296 months to 2 years0.260.20>2 years to 5 years0.140.116 to 12 years0.080.06Based on: Gibbs & Watts , Barratt et al , Morgenstern et al , von Schnakenburg et al 1. Urine Ox/Cr ratios are higher in very premature infants than in term infants, especially when they are receiving parenteral nutrition containing amino acids. The ratio falls when premature infants are receiving only glucose and electrolyte solutions .2. When very high dietary oxalate or low dietary calcium is suspected as the cause of the hyperoxaluria, the diet should be corrected and the urine oxalate remeasured for verification.Molecular Genetic FindingsDiagnostic findings are bi | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. genstern et al , von Schnakenburg et al 1. Urine Ox/Cr ratios are higher in very premature infants than in term infants, especially when they are receiving parenteral nutrition containing amino acids. The ratio falls when premature infants are receiving only glucose and electrolyte solutions .2. When very high dietary oxalate or low dietary calcium is suspected as the cause of the hyperoxaluria, the diet should be corrected and the urine oxalate remeasured for verification.Molecular Genetic FindingsDiagnostic findings are biallelic (homozygous or compound heterozygous) pathogenic variants in HOGA1 (see Table 2).Molecular testing approaches can include a
multigene panel and more comprehensive
genomic testing.Multigene panel. Because of the overlapping phenotypes of the three types of primary hyperoxaluria (see Differential Diagnosis), the authors recommend sequencing the coding and flanking intronic regions of AGXT (PH1), GRHPR (PH2), and HOGA1 ( | [
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] |
gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. .Molecular Genetic FindingsDiagnostic findings are biallelic (homozygous or compound heterozygous) pathogenic variants in HOGA1 (see Table 2).Molecular testing approaches can include a
multigene panel and more comprehensive
genomic testing.Multigene panel. Because of the overlapping phenotypes of the three types of primary hyperoxaluria (see Differential Diagnosis), the authors recommend sequencing the coding and flanking intronic regions of AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3) .If only one or no pathogenic variant is detected in one of these three genes in an individual whose clinical and laboratory findings strongly suggest PH, gene-targeted deletion/duplication analysis should be performed . The finding of only a single pathogenic variant should not be considered diagnostic without additional biochemical evidence (e.g., elevated HOG and DHG).For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests | [
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] |
gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. PH2), and HOGA1 (PH3) .If only one or no pathogenic variant is detected in one of these three genes in an individual whose clinical and laboratory findings strongly suggest PH, gene-targeted deletion/duplication analysis should be performed . The finding of only a single pathogenic variant should not be considered diagnostic without additional biochemical evidence (e.g., elevated HOG and DHG).For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.More comprehensive genomic testing, which may be used if no pathogenic variant is detected on a panel of the three PH-related genes, includes a multigene panel for a wide range of kidney stone-associated diseases and exome sequencing.For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.Table 2. Molecular Genetic Testing Used in Primary Hyperoxaluria Type 3View in own window | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. . More detailed information for clinicians ordering genetic tests can be found here.More comprehensive genomic testing, which may be used if no pathogenic variant is detected on a panel of the three PH-related genes, includes a multigene panel for a wide range of kidney stone-associated diseases and exome sequencing.For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.Table 2. Molecular Genetic Testing Used in Primary Hyperoxaluria Type 3View in own windowGene 1MethodProportion of Probands with a Pathogenic Variant Detectable by MethodHOGA1Sequence analysis 2All pathogenic variants reported to date 3Gene-targeted deletion/duplication analysis 4Unknown (i.e., no data on gene-targeted del/dup analysis are available)1. See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.2. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. Hyperoxaluria Type 3View in own windowGene 1MethodProportion of Probands with a Pathogenic Variant Detectable by MethodHOGA1Sequence analysis 2All pathogenic variants reported to date 3Gene-targeted deletion/duplication analysis 4Unknown (i.e., no data on gene-targeted del/dup analysis are available)1. See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.2. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.3. Belostotsky et al , Williams et al , Beck et al , Hopp et al | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. allelic variants detected in this gene.2. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.3. Belostotsky et al , Williams et al , Beck et al , Hopp et al 4. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and gene-targeted microarray designed to detect single-exon deletions or duplications.Clinical CharacteristicsClinical DescriptionIndividuals with primary hyperoxaluria type 3 (PH3) most often present in childhood with signs or symptoms related to kidney stones including hematuria, frequent ur | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. , Beck et al , Hopp et al 4. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and gene-targeted microarray designed to detect single-exon deletions or duplications.Clinical CharacteristicsClinical DescriptionIndividuals with primary hyperoxaluria type 3 (PH3) most often present in childhood with signs or symptoms related to kidney stones including hematuria, frequent urination, dysuria, blood visible in the urine, or pain associated with a stone.Although the stones are likely to be discovered due to symptoms, they may be detected incidentally on imaging studies performed for other purposes.Approximately 50%-65% of individuals with PH3 present with a stone prior to age five years . Although the frequency and severity of stone activity appear to abate in adolescence and adulthood , stone formation can occur throughout life, and some adults | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. related to kidney stones including hematuria, frequent urination, dysuria, blood visible in the urine, or pain associated with a stone.Although the stones are likely to be discovered due to symptoms, they may be detected incidentally on imaging studies performed for other purposes.Approximately 50%-65% of individuals with PH3 present with a stone prior to age five years . Although the frequency and severity of stone activity appear to abate in adolescence and adulthood , stone formation can occur throughout life, and some adults have many stones.Nephrocalcinosis has been reported to date only occasionally in individuals with PH3 .Over time, kidney function may become compromised from frequent stones and/or nephrocalcinosis, resulting in chronic kidney disease (CKD). However, kidney function appears to remain better preserved among individuals with PH3 compared to those with PH1 or PH2 .To date, only one individual with PH3 has been reported to progress to end-stage renal disease | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. formation can occur throughout life, and some adults have many stones.Nephrocalcinosis has been reported to date only occasionally in individuals with PH3 .Over time, kidney function may become compromised from frequent stones and/or nephrocalcinosis, resulting in chronic kidney disease (CKD). However, kidney function appears to remain better preserved among individuals with PH3 compared to those with PH1 or PH2 .To date, only one individual with PH3 has been reported to progress to end-stage renal disease. In this eight-year-old patient, stone removal procedures and urinary tract obstruction may have contributed to the loss of kidney function .Systemic oxalosis. The plasma concentration of oxalate increases significantly in individuals with PH and advanced CKD. When the plasma oxalate concentration reaches super-saturation, calcium oxalate crystals are deposited in many body tissues. Crystal-induced injury can include cutaneous ulcers, vascular disease, cardiomyopathy, cardiac conduction disturbances, non-healing fractures, erythropoietin- | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. reported to progress to end-stage renal disease. In this eight-year-old patient, stone removal procedures and urinary tract obstruction may have contributed to the loss of kidney function .Systemic oxalosis. The plasma concentration of oxalate increases significantly in individuals with PH and advanced CKD. When the plasma oxalate concentration reaches super-saturation, calcium oxalate crystals are deposited in many body tissues. Crystal-induced injury can include cutaneous ulcers, vascular disease, cardiomyopathy, cardiac conduction disturbances, non-healing fractures, erythropoietin-resistant anemia, and retinal deposits . Although systemic oxalosis is well recognized in PH1 and seen occasionally in PH2, it has not been reported to date in PH3, an observation consistent with the infrequency of end-stage renal disease (ESRD) in PH3.Heterozygotes. Although some heterozygotes (carriers) have had elevations of urinary oxalate , this may be coincidental as it is not seen in the majority. As more families are studied, additional | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. disturbances, non-healing fractures, erythropoietin-resistant anemia, and retinal deposits . Although systemic oxalosis is well recognized in PH1 and seen occasionally in PH2, it has not been reported to date in PH3, an observation consistent with the infrequency of end-stage renal disease (ESRD) in PH3.Heterozygotes. Although some heterozygotes (carriers) have had elevations of urinary oxalate , this may be coincidental as it is not seen in the majority. As more families are studied, additional information is expected to provide a better understanding of the risk to heterozygotes.Genotype-Phenotype CorrelationsAlthough no differences in phenotypic manifestations were noted among individuals with the two most common HOGA1 pathogenic variants , the relatively recent discovery of mutation of HOGA1 as the cause of PH3 and the rarity of PH3 (<100 affected individuals described to date) have limited this type of analysis.Families of Ashkenazi Jewish heritage | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. majority. As more families are studied, additional information is expected to provide a better understanding of the risk to heterozygotes.Genotype-Phenotype CorrelationsAlthough no differences in phenotypic manifestations were noted among individuals with the two most common HOGA1 pathogenic variants , the relatively recent discovery of mutation of HOGA1 as the cause of PH3 and the rarity of PH3 (<100 affected individuals described to date) have limited this type of analysis.Families of Ashkenazi Jewish heritage with PH3 have developed hypercalciuria in addition to hyperoxaluria ; however, to date no specific genotype-phenotype correlation has been established .PrevalenceSurveys of clinicians in central Europe led to estimates of the prevalence of primary hyperoxaluria (of all causes) of 1-3 per million population .Among individuals with primary hyperoxaluria approximately 70% have PH1, 10% have PH2, 10% have PH3, and 10% | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. of Ashkenazi Jewish heritage with PH3 have developed hypercalciuria in addition to hyperoxaluria ; however, to date no specific genotype-phenotype correlation has been established .PrevalenceSurveys of clinicians in central Europe led to estimates of the prevalence of primary hyperoxaluria (of all causes) of 1-3 per million population .Among individuals with primary hyperoxaluria approximately 70% have PH1, 10% have PH2, 10% have PH3, and 10% have no as-yet identified genetic cause .Registry data of the Rare Kidney Stone Consortium and OxalEurope suggest a prevalence of PH3 that is similar to PH2 and approximately one sixth that of PH1.By contrast, estimates from publicly available population data (NHLBI ESP) showed a PH3 carrier frequency of 1:185 , which was similar to the rate observed for PH1, suggesting certain individuals with PH3 either remain undiagnosed or do not | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. 10% have PH3, and 10% have no as-yet identified genetic cause .Registry data of the Rare Kidney Stone Consortium and OxalEurope suggest a prevalence of PH3 that is similar to PH2 and approximately one sixth that of PH1.By contrast, estimates from publicly available population data (NHLBI ESP) showed a PH3 carrier frequency of 1:185 , which was similar to the rate observed for PH1, suggesting certain individuals with PH3 either remain undiagnosed or do not have clinical manifestations. Prevalence of PH3 from the genomic data is currently estimated at 1:136,000 .PH3 has been observed more commonly among individuals of Ashkenazi Jewish descent ; however, the true prevalence in this population is unknown.Differential DiagnosisAny condition that causes calcium oxalate kidney stone disease or nephrocalcinosis and is associated with hyperoxaluria should be included in the differential diagnosis of primary hyperoxaluria type 3 (PH3) | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. with PH3 either remain undiagnosed or do not have clinical manifestations. Prevalence of PH3 from the genomic data is currently estimated at 1:136,000 .PH3 has been observed more commonly among individuals of Ashkenazi Jewish descent ; however, the true prevalence in this population is unknown.Differential DiagnosisAny condition that causes calcium oxalate kidney stone disease or nephrocalcinosis and is associated with hyperoxaluria should be included in the differential diagnosis of primary hyperoxaluria type 3 (PH3).Primary HyperoxaluriasThe three known types of primary hyperoxaluria (PH) are PH1 (due to mutation of AGXT), PH2 (mutation of GRHPR), and PH3 (mutation of HOGA1). Each gene encodes an enzyme for different metabolic pathways relevant for the metabolism of glyoxylate . Oxalate accumulates as an end product in all forms of PH; however, the specific pathways that lead to its accumulation | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. hyperoxaluria type 3 (PH3).Primary HyperoxaluriasThe three known types of primary hyperoxaluria (PH) are PH1 (due to mutation of AGXT), PH2 (mutation of GRHPR), and PH3 (mutation of HOGA1). Each gene encodes an enzyme for different metabolic pathways relevant for the metabolism of glyoxylate . Oxalate accumulates as an end product in all forms of PH; however, the specific pathways that lead to its accumulation in PH3 require further clarification .Of the primary hyperoxalurias, approximately 70% are PH1, 10% are PH2, 10% PH3, and 10% do not have an identified genetic cause . The clinical manifestations of the three known types of PH overlap considerably.In some individuals with PH3, significant stone manifestations have been observed in infancy and early childhood; these appear to have abated by later childhood or adolescence .Urine oxalate excretion | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. , the specific pathways that lead to its accumulation in PH3 require further clarification .Of the primary hyperoxalurias, approximately 70% are PH1, 10% are PH2, 10% PH3, and 10% do not have an identified genetic cause . The clinical manifestations of the three known types of PH overlap considerably.In some individuals with PH3, significant stone manifestations have been observed in infancy and early childhood; these appear to have abated by later childhood or adolescence .Urine oxalate excretion rates tend to be lower in individuals with PH3 than in those with PH1 or PH2 . In PH3 urine oxalate excretion appears to be more variable over time. However, because of the overlap of urinary oxalate excretion in all three types, the type of PH (and thus the diagnosis of PH3) cannot be confirmed on this basis alone .Hypercalciuria, observed in a subset of individuals with PH3, is not usually observed in PH | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. by later childhood or adolescence .Urine oxalate excretion rates tend to be lower in individuals with PH3 than in those with PH1 or PH2 . In PH3 urine oxalate excretion appears to be more variable over time. However, because of the overlap of urinary oxalate excretion in all three types, the type of PH (and thus the diagnosis of PH3) cannot be confirmed on this basis alone .Hypercalciuria, observed in a subset of individuals with PH3, is not usually observed in PH1 and PH2 .Hyperoxaluria of the degree observed in individuals with primary hyperoxaluria causes deposition of calcium oxalate crystals in the kidney (nephrocalcinosis) associated with inflammation, kidney damage, and often chronic kidney disease and/or end-stage renal disease (ESRD). ESRD appears to be unusual in PH3, having been reported in just one individual to date ; however, modest renal impairment has been described in other cohorts .Systemic calcium oxalate | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. PH3, is not usually observed in PH1 and PH2 .Hyperoxaluria of the degree observed in individuals with primary hyperoxaluria causes deposition of calcium oxalate crystals in the kidney (nephrocalcinosis) associated with inflammation, kidney damage, and often chronic kidney disease and/or end-stage renal disease (ESRD). ESRD appears to be unusual in PH3, having been reported in just one individual to date ; however, modest renal impairment has been described in other cohorts .Systemic calcium oxalate deposition (systemic oxalosis) may develop due to high levels of plasma oxalate in patients with PH who have advanced CKD. Systemic oxalosis results in varying degrees of organ dysfunction including infiltrative cardiomyopathy, arrhythmias due to involvement of the cardiac conduction system, erythropoietin-resistant anemia due to extensive crystal deposition in the bone marrow, pathologic fractures, and/or retinal oxalate deposition . Systemic oxalosis has not yet been reported in any individual with PH3, an observation consistent with | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. been described in other cohorts .Systemic calcium oxalate deposition (systemic oxalosis) may develop due to high levels of plasma oxalate in patients with PH who have advanced CKD. Systemic oxalosis results in varying degrees of organ dysfunction including infiltrative cardiomyopathy, arrhythmias due to involvement of the cardiac conduction system, erythropoietin-resistant anemia due to extensive crystal deposition in the bone marrow, pathologic fractures, and/or retinal oxalate deposition . Systemic oxalosis has not yet been reported in any individual with PH3, an observation consistent with the infrequency of end-stage renal disease (ESRD) in PH3.Differences in urinary metabolites other than oxalate can provide clues regarding the most likely type of PH.4-hydroxy-2-oxoglutarate (HOG). In PH3 urinary levels of HOG are often high, whereas in PH1 and PH2 urinary HOG is undetectable . The diagnostic sensitivity and specificity of this finding remain to be determined .Urinary glycolate may be | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. individual with PH3, an observation consistent with the infrequency of end-stage renal disease (ESRD) in PH3.Differences in urinary metabolites other than oxalate can provide clues regarding the most likely type of PH.4-hydroxy-2-oxoglutarate (HOG). In PH3 urinary levels of HOG are often high, whereas in PH1 and PH2 urinary HOG is undetectable . The diagnostic sensitivity and specificity of this finding remain to be determined .Urinary glycolate may be elevated in PH1 or occasionally in PH3 .Urine glycerate is increased in most individuals with PH2; however, exceptions (perhaps related to the sensitivity of the testing process) occur .See Primary hyperoxaluria: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.Idiopathic calcium oxalate stone disease can be associated with mild hyperoxaluria. The hyperoxaluria is typically of a lesser degree (<0.6 mmol | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. to be determined .Urinary glycolate may be elevated in PH1 or occasionally in PH3 .Urine glycerate is increased in most individuals with PH2; however, exceptions (perhaps related to the sensitivity of the testing process) occur .See Primary hyperoxaluria: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.Idiopathic calcium oxalate stone disease can be associated with mild hyperoxaluria. The hyperoxaluria is typically of a lesser degree (<0.6 mmol/day) than that observed in the primary hyperoxalurias, is variable from one collection to the next, and is frequently associated with mild hypercalciuria.Secondary HyperoxaluriasSecondary forms of hyperoxaluria are not uncommon and should be systematically considered.Dietary or other sources of excessive oxalate or oxalate precursors should be considered in the differential diagnosis. Very high doses of vitamin C are a potential cause. Exposure to toxins such as ethylene glycol can | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. degree (<0.6 mmol/day) than that observed in the primary hyperoxalurias, is variable from one collection to the next, and is frequently associated with mild hypercalciuria.Secondary HyperoxaluriasSecondary forms of hyperoxaluria are not uncommon and should be systematically considered.Dietary or other sources of excessive oxalate or oxalate precursors should be considered in the differential diagnosis. Very high doses of vitamin C are a potential cause. Exposure to toxins such as ethylene glycol can cause marked hyperoxaluria and associated acute renal failure.Enteric hyperoxaluria results from any cause of fat malabsorption in the small intestine. In the colon, this undigested fat combines with calcium and decreases the amount of calcium available to bind to oxalate. This free oxalate is absorbed. In addition, fatty acids that are not absorbed in the small intestine can damage the colonic mucosa, leading to further increase in oxalate absorption. Thus, any gastrointestinal disease or surgery | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. . Exposure to toxins such as ethylene glycol can cause marked hyperoxaluria and associated acute renal failure.Enteric hyperoxaluria results from any cause of fat malabsorption in the small intestine. In the colon, this undigested fat combines with calcium and decreases the amount of calcium available to bind to oxalate. This free oxalate is absorbed. In addition, fatty acids that are not absorbed in the small intestine can damage the colonic mucosa, leading to further increase in oxalate absorption. Thus, any gastrointestinal disease or surgery that impairs fat absorption is a potential cause of enteric hyperoxaluria . Hyperoxaluria resulting from short bowel syndrome and following malabsorptive types of gastric bypass surgery can be quite marked, overlapping the range seen in inherited PH of all types.Medications that interfere with fat absorption from the GI tract (e.g., orlistat) can be associated with hyperoxaluria.Marked deficiency of dietary calcium, leaving a greater proportion of oxalate free in the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. absorption. Thus, any gastrointestinal disease or surgery that impairs fat absorption is a potential cause of enteric hyperoxaluria . Hyperoxaluria resulting from short bowel syndrome and following malabsorptive types of gastric bypass surgery can be quite marked, overlapping the range seen in inherited PH of all types.Medications that interfere with fat absorption from the GI tract (e.g., orlistat) can be associated with hyperoxaluria.Marked deficiency of dietary calcium, leaving a greater proportion of oxalate free in the intestinal lumen, can result in increased absorption of oxalate resulting in hyperoxaluria.Nephrocalcinosis of prematurity occurs in a significant proportion of infants born prior to 28 weeks' gestation and is characterized by both nephrocalcinosis and nephrolithiasis . Risk factors among premature infants thought to contribute to this disease include urine oxalate that is higher than that observed in infants born at term as well as hypercalciuria and hypocitric aciduria. Calcium oxalate crystals have been | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. leaving a greater proportion of oxalate free in the intestinal lumen, can result in increased absorption of oxalate resulting in hyperoxaluria.Nephrocalcinosis of prematurity occurs in a significant proportion of infants born prior to 28 weeks' gestation and is characterized by both nephrocalcinosis and nephrolithiasis . Risk factors among premature infants thought to contribute to this disease include urine oxalate that is higher than that observed in infants born at term as well as hypercalciuria and hypocitric aciduria. Calcium oxalate crystals have been detected in the renal parenchyma . Since individuals with PH3 can develop stones in infancy or during early childhood , there may be confusion with stones or nephrocalcinosis related to prematurity.ManagementEvaluations Following Initial DiagnosisTo establish the extent of disease and needs in an individual diagnosed with primary hyperoxaluria type 3 (PH3), the following evaluations are recommended:Kidney imaging for assessment of number and location of stones and presence of nephrocalcinosisMeasurement of plasma | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. ic aciduria. Calcium oxalate crystals have been detected in the renal parenchyma . Since individuals with PH3 can develop stones in infancy or during early childhood , there may be confusion with stones or nephrocalcinosis related to prematurity.ManagementEvaluations Following Initial DiagnosisTo establish the extent of disease and needs in an individual diagnosed with primary hyperoxaluria type 3 (PH3), the following evaluations are recommended:Kidney imaging for assessment of number and location of stones and presence of nephrocalcinosisMeasurement of plasma oxalate concentration to assess the degree of oxalate overproductionBaseline 24-hour collection with measurement of oxalate, calcium, citrate, pH, urine volume, and other components of a supersaturation profile to identify specific risk factors for stones – information that is valuable in guiding treatmentAssessment of kidney function by serum creatinine and eGFRIf chronic kidney disease (CKD) is present, evaluation for signs of systemic oxalosis by physical examination (livedo reticularis or non | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. presence of nephrocalcinosisMeasurement of plasma oxalate concentration to assess the degree of oxalate overproductionBaseline 24-hour collection with measurement of oxalate, calcium, citrate, pH, urine volume, and other components of a supersaturation profile to identify specific risk factors for stones – information that is valuable in guiding treatmentAssessment of kidney function by serum creatinine and eGFRIf chronic kidney disease (CKD) is present, evaluation for signs of systemic oxalosis by physical examination (livedo reticularis or non-healing ulcers of the skin), echocardiography (oxalate cardiomyopathy), electrocardiogram (conduction disturbances), complete blood count (erythropoietin-resistant anemia), bone films (sclerosis, pathologic fractures due to oxalate osteodystrophy), and retinal examination (retinal oxalate deposits)Consultation with a clinical geneticist and/or genetic counselorTreatment of ManifestationsReduction of urine supersaturation of calcium oxalate in order to reduce stone formation and formation of calcium oxalate crystals that can be | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. physical examination (livedo reticularis or non-healing ulcers of the skin), echocardiography (oxalate cardiomyopathy), electrocardiogram (conduction disturbances), complete blood count (erythropoietin-resistant anemia), bone films (sclerosis, pathologic fractures due to oxalate osteodystrophy), and retinal examination (retinal oxalate deposits)Consultation with a clinical geneticist and/or genetic counselorTreatment of ManifestationsReduction of urine supersaturation of calcium oxalate in order to reduce stone formation and formation of calcium oxalate crystals that can be injurious to the kidney:Maintainance of high oral fluid intake (>2.5 L/m2 BSA)Oral administration of an inhibitor of calcium oxalate crystallization. Most patients are treated with one of these agents, which include potassium and sodium citrate , orthophosphate , or magnesium . Note: Simultaneous administration of citrate and phosphate should be done with caution due to the potential for increasing calcium phosphate supersaturation.Avoidance of supersaturation of calcium | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. and formation of calcium oxalate crystals that can be injurious to the kidney:Maintainance of high oral fluid intake (>2.5 L/m2 BSA)Oral administration of an inhibitor of calcium oxalate crystallization. Most patients are treated with one of these agents, which include potassium and sodium citrate , orthophosphate , or magnesium . Note: Simultaneous administration of citrate and phosphate should be done with caution due to the potential for increasing calcium phosphate supersaturation.Avoidance of supersaturation of calcium oxalate in the blood. Although there is little experience with chronic kidney disease in PH3, a decline in GFR to less than approximately 40 mL/min/1.73m2 would be expected to result in increased plasma oxalate and the potential for systemic oxalosis (as in other forms of PH). If plasma oxalate exceeds 35-50 μmol/L dialysis or transplantation is needed to reduce the risk of multiorgan complications of calcium oxalate deposition.Prevention of stone | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. supersaturation.Avoidance of supersaturation of calcium oxalate in the blood. Although there is little experience with chronic kidney disease in PH3, a decline in GFR to less than approximately 40 mL/min/1.73m2 would be expected to result in increased plasma oxalate and the potential for systemic oxalosis (as in other forms of PH). If plasma oxalate exceeds 35-50 μmol/L dialysis or transplantation is needed to reduce the risk of multiorgan complications of calcium oxalate deposition.Prevention of stone complications through regular monitoring (see Surveillance) and prompt attention to the following, any of which can damage kidney function:Alleviate obstruction of the urinary tract by a stone promptly through stent placement and/or stone removal.Maintain continuous fluid intake and urine flow before, during, and for several days after stone removal procedures.Treat urinary tract infections promptly and thoroughly, as bacteria may cause pyelonephritis or infect stones and complicate management.Avoidance of acute kidney injury by avoiding intravascular volume | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. complications of calcium oxalate deposition.Prevention of stone complications through regular monitoring (see Surveillance) and prompt attention to the following, any of which can damage kidney function:Alleviate obstruction of the urinary tract by a stone promptly through stent placement and/or stone removal.Maintain continuous fluid intake and urine flow before, during, and for several days after stone removal procedures.Treat urinary tract infections promptly and thoroughly, as bacteria may cause pyelonephritis or infect stones and complicate management.Avoidance of acute kidney injury by avoiding intravascular volume contraction at all times. This may necessitate intravenous fluids during severe gastroenteritis or other circumstances in which oral fluid intake cannot be maintained.Avoidance of marked dietary oxalate excess. Since the source of the excess oxalate in PH3 is metabolic overproduction, little is gained by strict low-oxalate diets, which in young children may compromise nutrition. Simple avoidance of marked dietary oxalate excess is recommended.Prevention of Primary ManifestationsSee Treatment of Manifestations.SurveillanceAttention to ongoing | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. Avoidance of acute kidney injury by avoiding intravascular volume contraction at all times. This may necessitate intravenous fluids during severe gastroenteritis or other circumstances in which oral fluid intake cannot be maintained.Avoidance of marked dietary oxalate excess. Since the source of the excess oxalate in PH3 is metabolic overproduction, little is gained by strict low-oxalate diets, which in young children may compromise nutrition. Simple avoidance of marked dietary oxalate excess is recommended.Prevention of Primary ManifestationsSee Treatment of Manifestations.SurveillanceAttention to ongoing care, including adherence to high fluid intake and medication schedule, is essential to good outcomes.For patients who are stable and doing well (see Note) the following are recommended annually:Clinical assessment of stone-related symptoms including pain, frequency of passage of stones or gravel in the urine, and urinary tract infectionAssessment of kidney function (serum creatinine and eGFR) and electrolytesMeasurement of plasma oxalate concentration, particularly in those with any impairment of glomerular | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. Treatment of Manifestations.SurveillanceAttention to ongoing care, including adherence to high fluid intake and medication schedule, is essential to good outcomes.For patients who are stable and doing well (see Note) the following are recommended annually:Clinical assessment of stone-related symptoms including pain, frequency of passage of stones or gravel in the urine, and urinary tract infectionAssessment of kidney function (serum creatinine and eGFR) and electrolytesMeasurement of plasma oxalate concentration, particularly in those with any impairment of glomerular filtration rate (GFR)24-hour urine oxalate and supersaturation study. During follow up, changes in the urine supersaturation can be used to monitor the effectiveness of therapy by confirming that the crystallization potential has decreased.Renal ultrasound examination or other imaging to monitor for stone formationNote: Very young patients, those with complex stone problems, and those with reduced kidney function need closer management with more frequent assessments.Agents/Circumstances to AvoidThe following should be avoided | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. , particularly in those with any impairment of glomerular filtration rate (GFR)24-hour urine oxalate and supersaturation study. During follow up, changes in the urine supersaturation can be used to monitor the effectiveness of therapy by confirming that the crystallization potential has decreased.Renal ultrasound examination or other imaging to monitor for stone formationNote: Very young patients, those with complex stone problems, and those with reduced kidney function need closer management with more frequent assessments.Agents/Circumstances to AvoidThe following should be avoided:Intravascular volume contraction (Note: Liberal use of intravenous fluids is indicated whenever oral fluid intake is inadequate.)Delays in treatment of acute stone episodesNephrotoxic agentsMarked dietary oxalate excessHigh-dose ascorbic acidEvaluation of Relatives at RiskUsing molecular genetic testing for the HOGA1 pathogenic variants found in the proband, it is appropriate to evaluate the older and younger sibs of a proband in order to identify as early as possible those | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. /Circumstances to AvoidThe following should be avoided:Intravascular volume contraction (Note: Liberal use of intravenous fluids is indicated whenever oral fluid intake is inadequate.)Delays in treatment of acute stone episodesNephrotoxic agentsMarked dietary oxalate excessHigh-dose ascorbic acidEvaluation of Relatives at RiskUsing molecular genetic testing for the HOGA1 pathogenic variants found in the proband, it is appropriate to evaluate the older and younger sibs of a proband in order to identify as early as possible those who would benefit from early treatment and preventive measures.Urine oxalate should be measured in all sibs who are affected (i.e., have biallelic HOGA1 pathogenic variants) or who are carriers (i.e., heterozygous for one HOGA1 pathogenic variant)Any sib with elevated urine oxalate/creatinine ratio or elevated oxalate excretion rate corrected for 1.73 m2 BSA should undergo kidney ultrasound examination, measurement of plasma oxalate concentration, a | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. in order to identify as early as possible those who would benefit from early treatment and preventive measures.Urine oxalate should be measured in all sibs who are affected (i.e., have biallelic HOGA1 pathogenic variants) or who are carriers (i.e., heterozygous for one HOGA1 pathogenic variant)Any sib with elevated urine oxalate/creatinine ratio or elevated oxalate excretion rate corrected for 1.73 m2 BSA should undergo kidney ultrasound examination, measurement of plasma oxalate concentration, a baseline 24-hour urine collection with a supersaturation profile, and measurement of serum creatinine concentration (see Evaluations Following Initial Diagnosis).See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Pregnancy ManagementThere have been no studies of pregnancy in women with PH3. However, most women with PH1 or PH2 who had good kidney function during pregnancy have done well and have delivered healthy infants .Adequate fluid intake should be | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. examination, measurement of plasma oxalate concentration, a baseline 24-hour urine collection with a supersaturation profile, and measurement of serum creatinine concentration (see Evaluations Following Initial Diagnosis).See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Pregnancy ManagementThere have been no studies of pregnancy in women with PH3. However, most women with PH1 or PH2 who had good kidney function during pregnancy have done well and have delivered healthy infants .Adequate fluid intake should be maintained throughout the pregnancy. Circumstances that compromise fluid intake, such as hyperemesis gravidarum, should prompt early initiation of IV fluid to maintain adequate hydration.Stones that become symptomatic during pregnancy may require routine (but specialized) techniques for management.In patients with stones, urinary tract infections should be treated promptly and thoroughly due to the potential for bacteria to cause pyelonephritis or infect stones and complicate management.Therapies Under InvestigationHumans cannot degrade oxalate; however | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. delivered healthy infants .Adequate fluid intake should be maintained throughout the pregnancy. Circumstances that compromise fluid intake, such as hyperemesis gravidarum, should prompt early initiation of IV fluid to maintain adequate hydration.Stones that become symptomatic during pregnancy may require routine (but specialized) techniques for management.In patients with stones, urinary tract infections should be treated promptly and thoroughly due to the potential for bacteria to cause pyelonephritis or infect stones and complicate management.Therapies Under InvestigationHumans cannot degrade oxalate; however, certain bacteria use oxalate as an energy source. Preliminary studies suggest that oral administration of O. formigenes could reduce oxalate excretion in individuals with PH. Two previous double-blind studies were inconclusive . A third clinical trial is under way in Europe, with results expected in 2015.Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK316514/ | Lx126Yq | Primary Hyperoxaluria Type 3 | C3150878 | 1 | primary hyperoxaluria type 3. Humans cannot degrade oxalate; however, certain bacteria use oxalate as an energy source. Preliminary studies suggest that oral administration of O. formigenes could reduce oxalate excretion in individuals with PH. Two previous double-blind studies were inconclusive . A third clinical trial is under way in Europe, with results expected in 2015.Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. | [
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omim | https://www.omim.org/entry/268250 | NgYmBq1 | RHIZOMELIC SYNDROME | C1849382 | 2 | rhizomelic syndrome. Urbach et al. (1986) described an inbred Arab family in which 1 female and 2 male sibs had symmetric and striking rhizomelia of the arms and other abnormalities of the skeleton (short stature, dislocated hips, digitalization of thumb with bifid distal phalanx), craniofacial structures (microcephaly, large anterior fontanel, micrognathia), and heart (pulmonic stenosis). All 3 sibs died in early childhood. In the endogamous Malay community of Cape Town, Viljoen et al. (1987) observed rhizomelic dysplasia in 3 sibs and in a first cousin once removed. Of the 2 individuals examined, 1 had prominent shortening of the humeri and the other of the femora. Seen alone, these might have been considered unrelated disorders. Al Gazali and Al-Asaad (1995) suggested that the boy with short, clublike femur reported by Viljo | [
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omim | https://www.omim.org/entry/268250 | NgYmBq1 | RHIZOMELIC SYNDROME | C1849382 | 2 | rhizomelic syndrome. the endogamous Malay community of Cape Town, Viljoen et al. (1987) observed rhizomelic dysplasia in 3 sibs and in a first cousin once removed. Of the 2 individuals examined, 1 had prominent shortening of the humeri and the other of the femora. Seen alone, these might have been considered unrelated disorders. Al Gazali and Al-Asaad (1995) suggested that the boy with short, clublike femur reported by Viljoen et al. (1987) actually had omodysplasia (258315).
Limbs
- Rhizomelia
- Digitalization of thumb
- Bifid distal phalanx of thumb
Skull
- Microcephaly
- Large anterior fontanel
- Micrognathia
Inheritance
- Autosomal recessive
Joints
- Dislocated hips
Growth
- Short stature
Cardiac
- Pulmonic stenosis
▲ Close | [
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] |
omim | https://www.omim.org/entry/268250 | NgYmBq1 | RHIZOMELIC SYNDROME | C1849382 | 2 | rhizomelic syndrome. like femur reported by Viljoen et al. (1987) actually had omodysplasia (258315).
Limbs
- Rhizomelia
- Digitalization of thumb
- Bifid distal phalanx of thumb
Skull
- Microcephaly
- Large anterior fontanel
- Micrognathia
Inheritance
- Autosomal recessive
Joints
- Dislocated hips
Growth
- Short stature
Cardiac
- Pulmonic stenosis
▲ Close | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. SummaryClinical characteristics.Primary trimethylaminuria is characterized by a fishy odor resembling that of rotten or decaying fish that results from excess excretion of trimethylamine in the urine, breath, sweat, and reproductive fluids. No physical symptoms are associated with trimethylaminuria. Affected individuals appear normal and healthy; however, the unpleasant odor often results in social and psychological problems. Symptoms are usually present from birth and may worsen during puberty. In females, symptoms are more severe just before and during menstruation, after taking oral contraceptives, and around the time of menopause.Diagnosis/testing.The diagnosis of primary trimethylaminuria is established in a proband who:Excretes (under normal dietary conditions) in the urine more than 10% of total trimethylamine (TMA) as the free amine; andHas biallelic (homozygous or compound heterozygous), known loss-of-function pathogenic variants in FMO3 on molecular genetic testing.Management.Treatment of manifestations: | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. severe just before and during menstruation, after taking oral contraceptives, and around the time of menopause.Diagnosis/testing.The diagnosis of primary trimethylaminuria is established in a proband who:Excretes (under normal dietary conditions) in the urine more than 10% of total trimethylamine (TMA) as the free amine; andHas biallelic (homozygous or compound heterozygous), known loss-of-function pathogenic variants in FMO3 on molecular genetic testing.Management.Treatment of manifestations:Dietary restriction of:Trimethylamine (present in milk obtained from wheat-fed cows) and its precursors including choline (present in eggs, liver, kidney, peas, beans, peanuts, soya products, and brassicas ), lecithin and lecithin-containing fish oil supplements;Trimethylamine N-oxide (present in seafood );Inhibitors of FMO3 enzyme activity such as indoles (found in brassicas).Note: Planning and monitoring of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. .Management.Treatment of manifestations:Dietary restriction of:Trimethylamine (present in milk obtained from wheat-fed cows) and its precursors including choline (present in eggs, liver, kidney, peas, beans, peanuts, soya products, and brassicas ), lecithin and lecithin-containing fish oil supplements;Trimethylamine N-oxide (present in seafood );Inhibitors of FMO3 enzyme activity such as indoles (found in brassicas).Note: Planning and monitoring of diet to ensure that the daily intake of choline and folate meets recommendations for age and sex; no restriction of dietary choline during pregnancy and lactation.Use of:Acid soaps and body lotions to remove secreted trimethylamine by washing;Activated charcoal and copper chlorophyllin to sequester trimethylamine produced in the gut;Antibiotics (metronidazole, amoxicillin, and neomycin) to suppress production of trimethylamine by reducing bacteria in the gut;Riboflavin supplements to enhance residual FMO3 enzyme | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. .Note: Planning and monitoring of diet to ensure that the daily intake of choline and folate meets recommendations for age and sex; no restriction of dietary choline during pregnancy and lactation.Use of:Acid soaps and body lotions to remove secreted trimethylamine by washing;Activated charcoal and copper chlorophyllin to sequester trimethylamine produced in the gut;Antibiotics (metronidazole, amoxicillin, and neomycin) to suppress production of trimethylamine by reducing bacteria in the gut;Riboflavin supplements to enhance residual FMO3 enzyme activity.Agents/circumstances to avoid: Foods with a high content of precursors of trimethylamine or inhibitors of FMO3 enzyme activity (seafoods: fish, cephalopods, and crustaceans), eggs, offal, legumes, brassicas, and soya products; food supplements and "health" foods that contain high doses of choline and lecithin; drugs metabolized by the enzyme FMO3; circumstances that promote sweating (e.g., exercise, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. supplements to enhance residual FMO3 enzyme activity.Agents/circumstances to avoid: Foods with a high content of precursors of trimethylamine or inhibitors of FMO3 enzyme activity (seafoods: fish, cephalopods, and crustaceans), eggs, offal, legumes, brassicas, and soya products; food supplements and "health" foods that contain high doses of choline and lecithin; drugs metabolized by the enzyme FMO3; circumstances that promote sweating (e.g., exercise, stress, emotional upsets).Evaluation of relatives at risk: Biochemical testing of sibs to identify those who are affected and will benefit from management to reduce production of trimethylamine.Genetic counseling.Primary trimethylaminuria is inherited in an autosomal recessive manner. The parents of an affected individual are obligate heterozygotes (i.e., presumed to be carriers of one FMO3 pathogenic variant based on family history). If both parents are known to be heterozygous for an FM | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. e.g., exercise, stress, emotional upsets).Evaluation of relatives at risk: Biochemical testing of sibs to identify those who are affected and will benefit from management to reduce production of trimethylamine.Genetic counseling.Primary trimethylaminuria is inherited in an autosomal recessive manner. The parents of an affected individual are obligate heterozygotes (i.e., presumed to be carriers of one FMO3 pathogenic variant based on family history). If both parents are known to be heterozygous for an FMO3 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the FMO3 pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.DiagnosisDiagnosis of primary trimethylaminuria has been discussed in detail and "best-practice" diagnostic | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. known to be heterozygous for an FMO3 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the FMO3 pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.DiagnosisDiagnosis of primary trimethylaminuria has been discussed in detail and "best-practice" diagnostic guidelines have been summarized .Suggestive FindingsPrimary trimethylaminuria should be suspected in individuals with the following clinical findings and family history.Body odor resembling that of rotten or decaying fish. Unoxidized trimethylamine (TMA) excreted in the urine, breath, sweat, and reproductive fluids is highly volatile and has a pungent ammoniac odor reminiscent of rotting fish .Note: Diagnosis of primary trimethylaminuria cannot be based on the examiner’ | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. and "best-practice" diagnostic guidelines have been summarized .Suggestive FindingsPrimary trimethylaminuria should be suspected in individuals with the following clinical findings and family history.Body odor resembling that of rotten or decaying fish. Unoxidized trimethylamine (TMA) excreted in the urine, breath, sweat, and reproductive fluids is highly volatile and has a pungent ammoniac odor reminiscent of rotting fish .Note: Diagnosis of primary trimethylaminuria cannot be based on the examiner’s sense of smell due to the following:The presence of the odor is often episodic and thus may not be noticeable when the person is examined.The human nose is normally very sensitive to trimethylamine, with some individuals being able to detect concentrations as low as 1 part in 109; however, olfactory testing is subjective and some people are unable to detect the smell of trimethylamine.The odor may be caused by compounds other than trimethylamine.Urinary excretion of trimethyl | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. ot be based on the examiner’s sense of smell due to the following:The presence of the odor is often episodic and thus may not be noticeable when the person is examined.The human nose is normally very sensitive to trimethylamine, with some individuals being able to detect concentrations as low as 1 part in 109; however, olfactory testing is subjective and some people are unable to detect the smell of trimethylamine.The odor may be caused by compounds other than trimethylamine.Urinary excretion of trimethylamine (TMA). Individuals complaining of or exhibiting a fishy odor should be tested for urinary excretion of TMA, ideally on two separate occasions . Although testing can be done under normal dietary conditions, it may help to consume a meal rich in choline (e.g., 2 eggs + 400 g "baked" or soya beans) prior to testing.Note: Because unaffected women may have transient trimethylaminuria at the onset of and during menstr | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. trimethylamine.Urinary excretion of trimethylamine (TMA). Individuals complaining of or exhibiting a fishy odor should be tested for urinary excretion of TMA, ideally on two separate occasions . Although testing can be done under normal dietary conditions, it may help to consume a meal rich in choline (e.g., 2 eggs + 400 g "baked" or soya beans) prior to testing.Note: Because unaffected women may have transient trimethylaminuria at the onset of and during menstruation , women should not be tested during this time frame.Urinary excretion of TMA is measured as one of the following:Percent of total trimethylamine (TMA) (i.e., free TMA plus the non-odorous metabolite TMA N-oxide) excreted in the urine as unmetabolized free TMA Severe trimethylaminuria: >40% of total TMA excreted as unmetabolized free TMAMild trimethylaminuria: 10%-39% | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. at the onset of and during menstruation , women should not be tested during this time frame.Urinary excretion of TMA is measured as one of the following:Percent of total trimethylamine (TMA) (i.e., free TMA plus the non-odorous metabolite TMA N-oxide) excreted in the urine as unmetabolized free TMA Severe trimethylaminuria: >40% of total TMA excreted as unmetabolized free TMAMild trimethylaminuria: 10%-39% of total TMA excreted as unmetabolized free TMAUnaffected: 0%-9% of total TMA excreted as unmetabolized free TMAConcentration of unmetabolized TMA in the urine. A urinary concentration of free TMA of 10 µg/mL (18-20 µmol/mmol creatinine) or higher, correlating with a urinary output of TMA of ~15-20 mg/day, appears to represent a threshold for the presence of the fishy body | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. uria: 10%-39% of total TMA excreted as unmetabolized free TMAUnaffected: 0%-9% of total TMA excreted as unmetabolized free TMAConcentration of unmetabolized TMA in the urine. A urinary concentration of free TMA of 10 µg/mL (18-20 µmol/mmol creatinine) or higher, correlating with a urinary output of TMA of ~15-20 mg/day, appears to represent a threshold for the presence of the fishy body odor associated with the disorder .Note: Currently available specific methods of detecting TMA and TMA N-oxide in urine involve sophisticated equipment and require skilled, experienced personnel. The methods used in mass spectrometry and proton NMR can detect TMA and TMA N-oxide simultaneously with great sensitivity. NMR has the additional advantage of requiring no prior extraction or separation of metabolites, making measurement possible directly on urine samples.Family history consistent with autosomal recessive inheritance (e.g., affected sibs | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. the presence of the fishy body odor associated with the disorder .Note: Currently available specific methods of detecting TMA and TMA N-oxide in urine involve sophisticated equipment and require skilled, experienced personnel. The methods used in mass spectrometry and proton NMR can detect TMA and TMA N-oxide simultaneously with great sensitivity. NMR has the additional advantage of requiring no prior extraction or separation of metabolites, making measurement possible directly on urine samples.Family history consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.Establishing the DiagnosisThe diagnosis of primary trimethylaminuria is established in a proband who:Excretes (under normal dietary conditions) in urine more than 10% of total trimethylamine (TMA) as the free amine; andHas biallelic (homozygous or compound heterozygous), known loss-of-function pathogenic variants in FMO3 identified on molecular genetic testing ( | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. .g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.Establishing the DiagnosisThe diagnosis of primary trimethylaminuria is established in a proband who:Excretes (under normal dietary conditions) in urine more than 10% of total trimethylamine (TMA) as the free amine; andHas biallelic (homozygous or compound heterozygous), known loss-of-function pathogenic variants in FMO3 identified on molecular genetic testing (see Table 1).Note: Identification of biallelic FMO3 variants of uncertain significance (or identification of one known FMO3 pathogenic variant and one FMO3 variant of uncertain significance) does not establish or rule out the diagnosis of this disorder.Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive
genomic testing (exome sequencing and genome sequencing) depending on the phenotype.Gene-targeted testing requires | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. O3 identified on molecular genetic testing (see Table 1).Note: Identification of biallelic FMO3 variants of uncertain significance (or identification of one known FMO3 pathogenic variant and one FMO3 variant of uncertain significance) does not establish or rule out the diagnosis of this disorder.Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive
genomic testing (exome sequencing and genome sequencing) depending on the phenotype.Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of primary trimethylaminuria has not been considered are more likely to be diagnosed using genomic testing (see Option 2).Option 1When the phenotypic and laboratory findings suggest the diagnosis of primary trimethylaminuria, molecular | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. phenotype.Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of primary trimethylaminuria has not been considered are more likely to be diagnosed using genomic testing (see Option 2).Option 1When the phenotypic and laboratory findings suggest the diagnosis of primary trimethylaminuria, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:Single-gene testing. Sequence analysis of FMO3 is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by the sequencing method used, the next | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. of primary trimethylaminuria, molecular genetic testing approaches can include single-gene testing or use of a multigene panel:Single-gene testing. Sequence analysis of FMO3 is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.A multigene panel that includes FMO3 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.A multigene panel that includes FMO3 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.Option 2When the diagnosis of primary trimethylaminuria has not been considered, comprehensive
genomic testing, which does not require the clinician to determine which gene is likely involved, is an option. Exome sequencing is most commonly used; genome sequencing is also possible.For an introduction to comprehensive genomic testing click here | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. , deletion/duplication analysis, and/or other non-sequencing-based tests.For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.Option 2When the diagnosis of primary trimethylaminuria has not been considered, comprehensive
genomic testing, which does not require the clinician to determine which gene is likely involved, is an option. Exome sequencing is most commonly used; genome sequencing is also possible.For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.Table 1. Molecular Genetic Testing Used in Primary TrimethylaminuriaView in own windowGene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by MethodFMO3Sequence analysis 3~99% 4Gene-targeted deletion/duplication analysis 5See footnote 6.1. See Table A. Genes and Databases for chromosome locus and protein.2. See Molecular Genetics for information | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.Table 1. Molecular Genetic Testing Used in Primary TrimethylaminuriaView in own windowGene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by MethodFMO3Sequence analysis 3~99% 4Gene-targeted deletion/duplication analysis 5See footnote 6.1. See Table A. Genes and Databases for chromosome locus and protein.2. See Molecular Genetics for information on allelic variants detected in this gene.3. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.4. Data derived from the subscription-based professional view of Human Gene | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. 2. See Molecular Genetics for information on allelic variants detected in this gene.3. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.4. Data derived from the subscription-based professional view of Human Gene Mutation Database 5. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.6. One individual with primary trimethylaminuria homozygous for a deletion of exons 1 and 2 has been reported . To date, this is the only FMO3 pathogenic variant reported to be | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. -based professional view of Human Gene Mutation Database 5. Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.6. One individual with primary trimethylaminuria homozygous for a deletion of exons 1 and 2 has been reported . To date, this is the only FMO3 pathogenic variant reported to be a large deletion.Clinical CharacteristicsDifferential DiagnosisMolecular diagnosis can distinguish primary trimethylaminuria from trimethylaminuria not caused by genetic FMO3 deficiency . A classification scheme for the latter has been proposed .Acquired trimethylaminuria emerges during adult life as a consequence of hepatitis in individuals with no previous personal history or familial history of the disorder. The metabolic changes persist after the liver problems have resolved, suggesting a permanent change in the expression or activity of the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. FMO3 pathogenic variant reported to be a large deletion.Clinical CharacteristicsDifferential DiagnosisMolecular diagnosis can distinguish primary trimethylaminuria from trimethylaminuria not caused by genetic FMO3 deficiency . A classification scheme for the latter has been proposed .Acquired trimethylaminuria emerges during adult life as a consequence of hepatitis in individuals with no previous personal history or familial history of the disorder. The metabolic changes persist after the liver problems have resolved, suggesting a permanent change in the expression or activity of the FMO3 enzyme.Transient childhood trimethylaminuria has been reported in preterm infants fed a choline-containing infant formula. Symptoms disappear as the children mature or when the choline source is discontinued . Young children who are heterozygous for a loss-of-function FMO3 pathogenic variant or have certain combinations of FMO3 variants (see Genotype-Phenotype Correlations) may exhibit mild symptoms of the disorder . Transient childhood forms are a consequence of the immaturity of FMO3 expression, which is | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. in the expression or activity of the FMO3 enzyme.Transient childhood trimethylaminuria has been reported in preterm infants fed a choline-containing infant formula. Symptoms disappear as the children mature or when the choline source is discontinued . Young children who are heterozygous for a loss-of-function FMO3 pathogenic variant or have certain combinations of FMO3 variants (see Genotype-Phenotype Correlations) may exhibit mild symptoms of the disorder . Transient childhood forms are a consequence of the immaturity of FMO3 expression, which is switched on after birth and continues to increase throughout childhood .Transient trimethylaminuria associated with menstruation. A short episode of trimethylaminuria can occur in women during menstruation . The effect is more pronounced in women homozygous for variants that result in a mild decrease in FMO3 enzyme activity .Precursor overload can cause a transient form of trimethylaminuria that results from saturation of the enzyme FMO3. It can occur in individuals with Huntington disease or Alzheimer disease who have been given | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. of FMO3 expression, which is switched on after birth and continues to increase throughout childhood .Transient trimethylaminuria associated with menstruation. A short episode of trimethylaminuria can occur in women during menstruation . The effect is more pronounced in women homozygous for variants that result in a mild decrease in FMO3 enzyme activity .Precursor overload can cause a transient form of trimethylaminuria that results from saturation of the enzyme FMO3. It can occur in individuals with Huntington disease or Alzheimer disease who have been given large oral therapeutic doses of choline (≥20 g/day) .Olfactory reference syndrome (ORS). In some individuals who perceive that they have a body odor, clinical investigation reveals that they do not have trimethylaminuria or other body-odor disorders, but rather the psychiatric disorder ORS . A distinguishing feature of ORS is its late onset.Disease statesLiver cirrhosis, impaired hepatocellular function, or the existence of portosystemic shunts may affect clearance of TMA absorbed from | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. or Alzheimer disease who have been given large oral therapeutic doses of choline (≥20 g/day) .Olfactory reference syndrome (ORS). In some individuals who perceive that they have a body odor, clinical investigation reveals that they do not have trimethylaminuria or other body-odor disorders, but rather the psychiatric disorder ORS . A distinguishing feature of ORS is its late onset.Disease statesLiver cirrhosis, impaired hepatocellular function, or the existence of portosystemic shunts may affect clearance of TMA absorbed from the gut. The resulting trimethylaminuria may contribute to the development of hepatic encephalopathy and coma and associated foetor hepaticus . In the case of congenital portosystemic shunt, manifestations of trimethylaminuria can be resolved by endovascular closure .In uremia, increased release of TMA from dietary precursors as a consequence of bacterial overgrowth in the small intestine, coupled with reduced renal clearance of TMA, can result in trimethylaminuria . The elevated blood concentration of TMA may contribute | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. may affect clearance of TMA absorbed from the gut. The resulting trimethylaminuria may contribute to the development of hepatic encephalopathy and coma and associated foetor hepaticus . In the case of congenital portosystemic shunt, manifestations of trimethylaminuria can be resolved by endovascular closure .In uremia, increased release of TMA from dietary precursors as a consequence of bacterial overgrowth in the small intestine, coupled with reduced renal clearance of TMA, can result in trimethylaminuria . The elevated blood concentration of TMA may contribute to nephritic neurologic conditions.Other causes of unpleasant body odor fall into two categories:Those not involving an increase of trimethylamine in the urine, including poor hygiene, gingivitis, and cases of blood-borne halitosis resulting from malodorous compounds other than trimethylamine. Another condition in this category is the rare metabolic disorder dimethylglycine dehydrogenase deficiency caused by biallelic pathogenic variants in DMGDH (OMIM 605850). Such conditions are distinguished by | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. elevated blood concentration of TMA may contribute to nephritic neurologic conditions.Other causes of unpleasant body odor fall into two categories:Those not involving an increase of trimethylamine in the urine, including poor hygiene, gingivitis, and cases of blood-borne halitosis resulting from malodorous compounds other than trimethylamine. Another condition in this category is the rare metabolic disorder dimethylglycine dehydrogenase deficiency caused by biallelic pathogenic variants in DMGDH (OMIM 605850). Such conditions are distinguished by low urinary TMA and a normal urinary TMA/TMA N-oxide ratio.Those resulting in an increase of trimethylamine in the urine, including urinary tract infections, bacterial vaginosis, advanced liver or kidney disease, and cervical cancer. In these cases, the TMA/TMA N-oxide ratio is normal, but affected individuals have large amounts of TMA in the urine. In contrast, primary trimethylaminuria, caused by FMO3 deficiency, is characterized by a high ratio | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. ). Such conditions are distinguished by low urinary TMA and a normal urinary TMA/TMA N-oxide ratio.Those resulting in an increase of trimethylamine in the urine, including urinary tract infections, bacterial vaginosis, advanced liver or kidney disease, and cervical cancer. In these cases, the TMA/TMA N-oxide ratio is normal, but affected individuals have large amounts of TMA in the urine. In contrast, primary trimethylaminuria, caused by FMO3 deficiency, is characterized by a high ratio of TMA/TMA N-oxide in the urine.ManagementNo clinical practice guidelines for primary trimethylaminuria have been published.Evaluations Following Initial DiagnosisTo establish the extent of disease and needs in an individual diagnosed with primary trimethylaminuria, the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:Determine the urinary ratio of trimethylamine (TMA) N-oxide to total TMA on a normal diet. The general rule is | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. , is characterized by a high ratio of TMA/TMA N-oxide in the urine.ManagementNo clinical practice guidelines for primary trimethylaminuria have been published.Evaluations Following Initial DiagnosisTo establish the extent of disease and needs in an individual diagnosed with primary trimethylaminuria, the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:Determine the urinary ratio of trimethylamine (TMA) N-oxide to total TMA on a normal diet. The general rule is that the lower the ratio the more severe the disorder:Ratios of 70%-89% are classified as mild.Ratios lower than 70% are classified as severe.Assess social issues associated with body odor. These may include harassment, bullying, discrimination, negative self-image, social isolation, and relationship problems . An assessment tool for evaluation of social and mental health effects of the disorder has been proposed .Consult with a medical geneticist, certified genetic counselor | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. normal diet. The general rule is that the lower the ratio the more severe the disorder:Ratios of 70%-89% are classified as mild.Ratios lower than 70% are classified as severe.Assess social issues associated with body odor. These may include harassment, bullying, discrimination, negative self-image, social isolation, and relationship problems . An assessment tool for evaluation of social and mental health effects of the disorder has been proposed .Consult with a medical geneticist, certified genetic counselor, or certified advanced genetic nurse to inform affected individuals and their families about the nature, mode of inheritance, and implications of primary trimethylaminuria in order to facilitate medical and personal decision making.Treatment of ManifestationsStrategies for the treatment of primary trimethylaminuria summarized in this section are reviewed by Schmidt & Leroux .Restriction of dietary trimethylamine and its precursors. In some instances the disorder can be successfully managed by dietary restriction of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. geneticist, certified genetic counselor, or certified advanced genetic nurse to inform affected individuals and their families about the nature, mode of inheritance, and implications of primary trimethylaminuria in order to facilitate medical and personal decision making.Treatment of ManifestationsStrategies for the treatment of primary trimethylaminuria summarized in this section are reviewed by Schmidt & Leroux .Restriction of dietary trimethylamine and its precursors. In some instances the disorder can be successfully managed by dietary restriction of precursors of trimethylamine. This is particularly true of "mild" or moderate forms of primary trimethylaminuria. Affected individuals respond differently to different forms of dietary restriction; thus, urinary excretion of trimethylamine and trimethylamine N-oxide should be monitored to identify the most effective dietary regimen for an individual.Dietary regimens should be planned and monitored to ensure that the daily intake of choline and folate meet recommendations for the age and sex of the individual . For adults, adequate daily | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. be successfully managed by dietary restriction of precursors of trimethylamine. This is particularly true of "mild" or moderate forms of primary trimethylaminuria. Affected individuals respond differently to different forms of dietary restriction; thus, urinary excretion of trimethylamine and trimethylamine N-oxide should be monitored to identify the most effective dietary regimen for an individual.Dietary regimens should be planned and monitored to ensure that the daily intake of choline and folate meet recommendations for the age and sex of the individual . For adults, adequate daily intake of choline is 550 mg for males and 425 mg for females.Choline is one of the most important dietary sources of trimethylamine. Dietary choline is absorbed through the small intestine; however, when the absorptive capacity of the small intestine is overloaded, gut bacteria metabolize choline into trimethylamine, which is readily absorbed into the blood stream.Foods rich in choline include eggs, liver, kidney, peas, beans, peanuts, soya products, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. individual . For adults, adequate daily intake of choline is 550 mg for males and 425 mg for females.Choline is one of the most important dietary sources of trimethylamine. Dietary choline is absorbed through the small intestine; however, when the absorptive capacity of the small intestine is overloaded, gut bacteria metabolize choline into trimethylamine, which is readily absorbed into the blood stream.Foods rich in choline include eggs, liver, kidney, peas, beans, peanuts, soya products, and brassicas (Brussels sprouts, broccoli, cabbage, cauliflower) as well as rapeseed products such as oil and flour.Nutritionally balanced, choline-restricted diets suitable for the treatment of trimethylaminuria have been developed .Because choline is essential in the fetus and in young infants for nerve and brain development, it should not be over-restricted in infants, children, and pregnant or lactating women. Large amounts of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. peanuts, soya products, and brassicas (Brussels sprouts, broccoli, cabbage, cauliflower) as well as rapeseed products such as oil and flour.Nutritionally balanced, choline-restricted diets suitable for the treatment of trimethylaminuria have been developed .Because choline is essential in the fetus and in young infants for nerve and brain development, it should not be over-restricted in infants, children, and pregnant or lactating women. Large amounts of choline are transferred to the fetus via the placenta and to the newborn infant via the mother's milk, thus potentially depleting maternal choline reserves. Dietary restriction of choline increases the requirement for folate, a methyl donor.Trimethylamine N-oxide. Affected individuals should avoid eating seafood (fish, cephalopods, and crustaceans) because of its high content of trimethylamine N-oxide, which is reduced to trimethylamine in the human gut. Babies with trimethyl | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. or lactating women. Large amounts of choline are transferred to the fetus via the placenta and to the newborn infant via the mother's milk, thus potentially depleting maternal choline reserves. Dietary restriction of choline increases the requirement for folate, a methyl donor.Trimethylamine N-oxide. Affected individuals should avoid eating seafood (fish, cephalopods, and crustaceans) because of its high content of trimethylamine N-oxide, which is reduced to trimethylamine in the human gut. Babies with trimethylaminuria who are breastfed after their mothers have eaten seafood may develop a fishy odor.Note: Freshwater fish have a lower content of trimethylamine N-oxide and thus are not a problem.Other. Milk obtained from wheat-fed cows may have significant amounts of trimethylamine and thus should be avoided.Affected individuals should avoid lecithin (an important dietary source of choline) and lecithin-containing fish oil supplements.In addition to being a source of trimethyl | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. the human gut. Babies with trimethylaminuria who are breastfed after their mothers have eaten seafood may develop a fishy odor.Note: Freshwater fish have a lower content of trimethylamine N-oxide and thus are not a problem.Other. Milk obtained from wheat-fed cows may have significant amounts of trimethylamine and thus should be avoided.Affected individuals should avoid lecithin (an important dietary source of choline) and lecithin-containing fish oil supplements.In addition to being a source of trimethylamine precursors, brassicas (Brussels sprouts, broccoli, cabbage, and cauliflower) contain indoles, which may inhibit FMO3 enzyme activity and thus increase urinary excretion of trimethylamine . Intake of such vegetables should be restricted.Use of acid soaps and body lotions. Trimethylamine is a strong base (pKa 9.8). Thus, at pH 6.0, less than 0.02% of trimethylamine | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. addition to being a source of trimethylamine precursors, brassicas (Brussels sprouts, broccoli, cabbage, and cauliflower) contain indoles, which may inhibit FMO3 enzyme activity and thus increase urinary excretion of trimethylamine . Intake of such vegetables should be restricted.Use of acid soaps and body lotions. Trimethylamine is a strong base (pKa 9.8). Thus, at pH 6.0, less than 0.02% of trimethylamine exists as the volatile free base. The use of soaps and body lotions with a pH close to that of normal skin (pH 5.5-6.5) helps retain secreted trimethylamine in a less volatile salt form that can be removed by washing.Sequestering of trimethylamine produced in the gut. When taken as dietary supplements, activated charcoal (750 mg 2x/day for 10 days) and copper chlorophyllin (60 mg 3x/day | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. 0.02% of trimethylamine exists as the volatile free base. The use of soaps and body lotions with a pH close to that of normal skin (pH 5.5-6.5) helps retain secreted trimethylamine in a less volatile salt form that can be removed by washing.Sequestering of trimethylamine produced in the gut. When taken as dietary supplements, activated charcoal (750 mg 2x/day for 10 days) and copper chlorophyllin (60 mg 3x/day after meals for 3 weeks) decrease the concentration of free trimethylamine in the urine .Suppression of intestinal production of trimethylamine. A short course of antibiotics to modulate or reduce the activity of gut microflora, and thus suppress the production of trimethylamine, is effective in some cases . Such treatment may be useful when dietary restriction needs to be relaxed (e.g., for important social occasions), or when trimethylamine production appears to increase (e.g., | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. (60 mg 3x/day after meals for 3 weeks) decrease the concentration of free trimethylamine in the urine .Suppression of intestinal production of trimethylamine. A short course of antibiotics to modulate or reduce the activity of gut microflora, and thus suppress the production of trimethylamine, is effective in some cases . Such treatment may be useful when dietary restriction needs to be relaxed (e.g., for important social occasions), or when trimethylamine production appears to increase (e.g., during menstruation, infection, emotional upset, stress, or exercise). Three antibiotics with different target organisms have been used: metronidazole, amoxicillin, and neomycin. Neomycin appears to be the most effective in preventing formation of trimethylamine from choline .Enhancement of residual FMO3 enzyme activity. Supplements of riboflavin, a precursor of the FAD prosthetic group of FMOs, may help maximize residual FMO3 enzyme activity . Recommended intake is 30-40 mg 3-5x/ | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. increase (e.g., during menstruation, infection, emotional upset, stress, or exercise). Three antibiotics with different target organisms have been used: metronidazole, amoxicillin, and neomycin. Neomycin appears to be the most effective in preventing formation of trimethylamine from choline .Enhancement of residual FMO3 enzyme activity. Supplements of riboflavin, a precursor of the FAD prosthetic group of FMOs, may help maximize residual FMO3 enzyme activity . Recommended intake is 30-40 mg 3-5x/day with food. Children given riboflavin should be monitored closely because excessive amounts may cause gastrointestinal distress.Counseling. Affected individuals and their families benefit from counseling. Realization that the problem is the result of a recognized medical condition may help. As well as receiving dietary advice, affected individuals should be advised that the condition may be exacerbated during menstruation and by factors that promote sweating, such as fever, exercise, stress, and emotional upsets.Assessment of efficacy of treatment. A | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. 40 mg 3-5x/day with food. Children given riboflavin should be monitored closely because excessive amounts may cause gastrointestinal distress.Counseling. Affected individuals and their families benefit from counseling. Realization that the problem is the result of a recognized medical condition may help. As well as receiving dietary advice, affected individuals should be advised that the condition may be exacerbated during menstruation and by factors that promote sweating, such as fever, exercise, stress, and emotional upsets.Assessment of efficacy of treatment. A tool for patient self-assessment of the effect of treatment on social and mental health aspects of the disorder has been proposed .Agents/Circumstances to AvoidThe following should be avoided:Foods with a high content of precursors of trimethylamine or inhibitors of FMO3 enzyme activity, including seafood (fish, cephalopods, and crustaceans), eggs, offal, legumes, brassicas, and soya products. Avoid or eat in moderation.Food supplements | [
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