bluuebunny/crossref_metadata_2025_split huggingface dataset:
Standardized loading test with protein for the differentiation of phenylketonuria from hyperphenylalaninaemia
Authors: Lutz P. , Schmidt H. , Frey G. , Bickel H. 
Published: June 2005

AbstractEighty‐nine protein‐loading tests were performed in 80 patients with an increased blood phenylalanine concentration. The amount of protein corresponding to 0.18g phenylalanine/kg body weight per day was calculated and given for 3 days, during which time eight phenylalanine and eight tyrosine blood concentrations were determined. Nine numerical evaluations were checked for discrimination between phenylketonuria and hyperphenylalaninaemia. The two most powerful discriminants were the phenylalanine blood concentration after 72 hours (sample taken in the morning of the 4th day after the beginning of the load) with a limit value of 15 mg/dl (0.91 mmol/l), and the mean value of the 5th to 8th phenylalanine values, also with a limit value of 15 mg/dl. In only eight of the 80 patients would the final diagnosis not have been established by the loading test.
Organic aciduria in neonatal multiple carboxylase deficiency
Authors: Sweetman L. , Nyhan W. L. , Sakati N. A. , Ohlsson A. , Mange M. S. , Boychuk R. B. , Kaye R. 
Published: June 2005

AbstractA Samoan patient and a Saudi‐Arabian patient were found to have abnormalities in the pattern of organic acid metabolites characteristic of 3‐methylcrotonylglycinuria, propionic acidaemia and lactic acidosis. Both patients died early in life. The metabolic pattern is diagnostic of multiple carboxylase deficiency and an enzymatic diagnosis was made in a subsequent affected sibling of the first patient. Deficiency of the three carboxylases suggests a primary defect in the metabolism of biotin which is required for their activity. The importance of the recognition of the clinical picture is highlighted by the fact that this lethal disease is readily treated with biotin. These patients have prominent skin lesions which can serve as alerting signs for the diagnosis.
Normal 2‐aminobutyrate oxidation and increased valine oxidation in fibroblasts deficient in pyruvate dehydrogenase
Authors: Borud O. , Pettersen J. E. 
Published: June 2005

AbstractHuman skin fibroblasts deficient in pyruvate dehydrogenase and five normal control strains were incubated with one of the following labelled substrates:dl‐[1‐14C]‐2‐amino‐n‐butyric acid,dl‐[3‐14C]‐2‐amino‐n‐butyric acid,dl‐[1‐14C]leucine,l‐[1‐14C]valine,l‐[1‐14C]alanine, and [1‐14C]pyruvate. The rate of14CO2‐production in the deficient cells was normal from 2‐aminobutyrate and leucine, increased from valine, and decreased from alanine and pyruvate. These results indicated that in human skin fibroblasts the decarboxylation of 2‐oxobutyrate is catalysed by an enzyme system different from the pyruvate dehydrogenase complex.
In vivo disposal of phenylalanine in phenylketonuria: A study of two siblings
Authors: Treacy E. , Pitt J. J. , Seller K. , Thompson G. N. , Ramus S. , Cotton R. G. H. 
Published: June 2005

SummaryMutation at the phenylalanine hydroxylase (PAH) locus is a cause of hyperphenylalaninaemia. Genotype‐phenotype correlation relative to the predicted PAH activity may differ at the metabolite level and at the IQ level in untreated phenylketonuria. Discordant metabolic phenotypes have been noted in siblings; influences on transport and metabolism of phenylalanine determining homeostasis may account for differing metabolic phenotypes. We report two siblings of different sex and identical genotype at the PAH locus who demonstrate a difference in phenylalanine disposal. A stable isotope infusion of [2H5]phenylalanine was used to measure protein turnover, phenylalanine hydroxylation and excretion of phenylalanine transamination metabolites. The siblings were observed to have identical hydroxylation rates under the experimental conditions of the study while manifesting differences in renal excretion rates of phenylalanine transamination metabolites and protein accretion.
A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency
Authors: Vreken P. , Van Kuilenburg A. B. P. , Meinsma R. , Smit G. P. A. , Bakker H. D. , De Abreu R. A. , van Gennip A. H. 
Published: June 2005

SummaryDihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterized by thymine‐uraciluria and associated with a variable clinical phenotype. In order to identify the molecular defect underlying complete DPD deficiency in a Dutch patient previously shown to have a 165 base pair deletion in the mature DPD mRNA, we cloned the genomic region encompassing the skipped exon and its flanking intron sequences. Sequence analysis revealed that the patient was homozygous for a single G→A point mutation in the invariant GT dinucleotide splice donor site downstream of the skipped exon. The same mutation was identified in another, unrelated, Dutch patient. Because this mutation destroys a uniqueMaeII restriction site, rapid screening using restriction enzyme cleavage of the amplified genomic region encompassing this mutation is possible. Analysis of 50 controls revealed no individuals heterozygous for this mutation
Bone marrow involvement and obstructive jaundice in Farber lipogranulomatosis: clinical and autopsy report of a new case
Authors: Nowaczyk M. J. M. , Feigenbaum A. , Silver M. M. , Callahan J. , Levin A. , Jay V. 
Published: June 2005

SummaryWe report a case of Farber lipogranulomatosis in a girl with hepatosplenomegaly, macular cherry‐red spot, and subcutaneous nodules who developed liver dysfunction with jaundice and ascites, and myelophthisic anaemia because of infiltration of bone marrow with storage cells. Acid ceramidase assay confirmed the diagnosis. We conclude that the bone marrow dysfunction and cherry‐red spot are features of type IV Farber lipogranulomatosis that have not been previously recognized, and should be added to the clinical phenotypic description.
NADH‐coenzyme Q reductase (complex I) deficiency: heterogeneity in phenotype and biochemical findings
Authors: Pitkanen S. , Feigenbaum A. , Laframboise R. , Robinson B. H. 
Published: June 2005

SummaryTwelve patient cell lines with biochemically proven complex I deficiency were compared for clinical presentation and outcome, together with their sensitivity to galactose and menadione toxicity. Each patient had elevated lactate to pyruvate ratios demonstrable in fibroblast cultures. Each patient also had decreased rotenone‐sensitive NADH‐cytochromec reductase (complexes I and III) with normal succinate cytochromec reductase (complexes II and III) and cytochrome oxidase (complex IV) activity in cultured skin fibroblasts, indicating a deficient NADH‐coenzyme Q reductase (complex I) activity. The patients fell into five categories: severe neonatal lactic acidosis; Leigh disease; cardiomyopathy and cataracts; hepatopathy and tubulopathy; and mild symptoms with lactic acidaemia. Cell lines from 4 out of the 12 patients were susceptible to both galactose and menadione toxicity and 3 of these also displayed low levels of ATP synthesis in digitonin‐permeabilized skin fibroblasts from a number of substrates. This study highlights the heterogeneity of complex I deficiency at the clinical and biochemical level.
Neutral lipid storage disease with ichthyosis: Lipid content and metabolism of fibroblasts
Authors: Williams M. L. , Monger D. J. , Rutherford S. L. , Hincenbergs M. , Rehfeld S. J. , Grunfeld C. 
Published: June 2005

SummaryNeutral lipid storage disease with ichthyosis is a newly recognized heritable disorder characterized by widespread cellular triglyceride storage. Lipid metabolism in fibroblasts cultured from three affected family members was studied. The stored lipid is triglyceride composed of an unremarkable fatty acid profile and derived from both exogenously‐supplied and endogenously‐synthesized fatty acids. Lipid storage could not be corrected by prolonged culture in lipid‐depleted media. Acetyl CoA carboxylase activity and β‐oxidation of palmitate were both normal. Taken together, these studies exclude a primary defect of fatty acid uptake, over‐synthesis or impaired β‐oxidation. Moreover, triacylglycerol lipase activity of homogenates of fibroblasts from patients with NLSDI examined over the range of pH 3.5–8.5 was normal.
Group work with adolescent PKU girls and their mothers
Authors: Cohen B. E. , Weiss R. , Hadar R. , Normand M. , Shiloh S. , Elhanati D. 
Published: June 2005

SummaryGroup therapy was the method chosen for working with PKU girls and their mothers in improving their knowledge of maternal PKU and the prevention of unplanned pregnancies. It was found effective in relieving anxiety, and the importance of including the mothers in the group was critical.
Rapid diagnosis of medium‐chain acyl CoA dehydrogenase deficiency by measurement ofcis‐4‐decenoic acid in plasma
Authors: Heales S. J. R. , Woolf D. A. , Robinson P. , Leonard J. V. 
Published: June 2005

SummaryPlasma concentrations of octanoate andcis‐4‐decenoate were measured by gas chromatography‐mass spectrometry in children with deficiencies of medium‐chain acyl‐CoA dehydrogenase (MCAD), long‐chain 3‐hydroxyacyl‐CoA dehydrogenase (3LHAD) and multiple acyl‐CoA dehydrogenase (MAD) deficiency. Children receiving medium‐ and long‐chain lipid supplements were also studied. Octanoate was elevated in all but one of the children with MCAD deficiency, in MAD deficiency and in children receiving medium‐chain triglyceride supplementation.Cis‐4‐decenoate was only elevated in MCAD and MAD deficiency. It is concluded that measurement of plasmacis‐4‐decenoate provides a sensitive and specific test for defects of medium‐chain acyl CoA dehydrogenase.
N‐acetylglutamate synthetase deficiency: Clinical and laboratory observations
Authors: Pandya A. L. , Koch R. , Hommes F. A. , Williams J. C. 
Published: June 2005

SummaryTwo male siblings presented in the first 6 weeks of life with emesis, diarrhoea, metabolic acidosis and lethargy. A male sibling had previously died at 14 months of age from liver failure of unknown aetiology. Both of the current cases had mild hyperammonaemia with normal orotic acid, organic acid and argininosuccinic acid levels. Citrulline and arginine levels were normal or mildly decreased. One of the brothers was biopsied and had no detectableN‐acetylglutamate synthetase activity and normal values for other enzymes of the urea cycle in liver. Treatment with a low‐protein diet and sodium benzoate/sodium phenylacetate resulted in near normal blood ammonia levels, except during viral illness. Subsequent neurological development has been normal to mildly delayed. These patients differ from those previously decribed withN‐acetylglutamate synthetase deficiency in that their presentation and subsequent course were relatively benign.
Possible deleterious effect ofL‐carnitine supplementation in a patient with mild multiple acyl‐CoA dehydrogenation deficiency (ethylmalonic‐adipic aciduria)
Authors: Green A. , Preece M. A. , de Sousa C. , Pollitt R. J. 
Published: June 2005

SummaryA patient with riboflavin‐responsive mild multiple acyl‐CoA dehydrogenation deficiency of the ethylmalonic‐adipic aciduria type experienced a recurrence of spontaneous hypoglycaemic episodes whilst being given supplementaryL‐cartinine. This phenomenon is explicable in terms of the known biochemical features of this condition and suggests caution in the carnitine supplementation of patients with defective oxidation of medium‐ or short‐chain fatty acyl‐CoA esters. This patient excreted excessive phenylpropionylglycine after an oral phenylpropionic acid load. Thus the phenylpropionic acid loading test is not completely specific for primary medium‐chain acyl‐CoA dehydrogenase deficiency as has been supposed.
Biochemical characterization of β‐hexosaminidase in different biological specimens from eleven patients with GM2‐gangliosidosis B1 variant
Authors: Ribeiro M. G. , Pinto R. A. , Dos Santos M. R. , Maia M. , Sá Miranda M. C. 
Published: June 2005

SummaryGM2‐gangliosidosis B1 variant is thought to be a rare disorder with a wide geographical and ethnic distribution. We report the biochemical findings obtained in different specimens from a group of 11 B1 variant patients originating from the north of Portugal. The biochemical data obtained seem to indicate that only one of these patients is a genetic compound presenting a clinical and biochemical pattern similar to the majority of B1 variant patients described in the literature, but somewhat different from the profile presented by the other patients reported here, who are homozygous for the ‘DN‐allele’.
Heterozygous carriers of classical phenylketonuria in a sample of the turkish population: Detection by a spectrofluorimetric method
Authors: Güneral F. , Özalp İ. , Tatlidil H. 
Published: June 2005

SummaryBlood obtained by finger prick from 209 presumed normal homozygotes and 42 heterozygotes for classical PKU was analysed for plasma phenylalanine (Phe) and tyrosine (Tyr) by a fluorimetric method. Subjects were tested near midday and 3 hours after a protein‐rich breakfast. The plot of Phe/Tyr (micromolar ratio) against Phe2/Tyr, permitted the detection of 11 heterozygotes among 209 controls. The accuracy of this method was checked by computation of a stepwise multivariate discriminant analysis, using Phe and Tyr (µmol/L), Phe/Tyr micromolar ratio and Phe2/Tyr as variables. Ten of the 11 subjects were recovered with a percentage of correct classification of over 90%, while one case had a percentage of 89.45%. The PKU gene frequency was found to be 1/19. This emphasizes the importance of a screening programme for PKU gene carrier status in Turkey.
Agoraphobia in phenylketonuria
Authors: Waisbren S. E. , Levy H. L. 
Published: June 2005

SummaryWe describe agoraphobia as a complication of phenylketonuria (PKU) in young adults. The five patients have classic PKU and received phenylalanine‐restricted diet only in childhood. Only one has normal intelligence. All but one were also depressed. All were anxious. Three of the five had initiated the phenylalanine‐restricted diet after 3 months of age. Two returned to the phenylalanine‐restricted diet with dramatic reduction of symptoms.The frequency of manifestations of agoraphobia was also examined in 50 young women with PKU enrolled in a longitudinal study of psychosocial factors in maternal PKU, 47 of their acquaintances and 49 women with diabetes. All were administered a test of agoraphobic‐avoidant behaviour. The women with PKU appeared to be more prone to social withdrawal and fear of leaving home. Twenty per cent were within the agoraphobia range of the Mobility Inventory. Those still on diet and those with non‐PKU hyperphenylalaninaemia reported less avoidant behaviour than those who had terminated the diet in childhood.These results suggest that young adults with PKU are at risk for agoraphobia but that return to the phenylalanine‐restricted diet may be an effective treatment.
Analbuminaemia: a natural model of metabolic compensatory systems
Authors: Baldo‐Enzi G. , Baiocchi M. R. , Vigna G. , Andrian C. , Mosconi C. , Fellin R. 
Published: June 2005

SummaryImportant clinical signs are usually not present in analbuminaemia, a congenital condition inherited as an autosomal recessive trait, but several biochemical alterations in proteins, cholesterol, phospholipids and plasma beta lipoproteins have been observed.We studied two sibs, R.U. and R.R., with this disease and observed a striking increase in the variables mentioned above as well as a high LDL fraction with concomitant increase in apo B; increases in HDL3 and apo A‐I and A‐II levels were also observed. The lipoproteins, however, were not altered in morphology but showed a slight increase in lipid/protein ratio. Post‐heparin lipolytic activity was normal in the male patient and reduced in the female while LCAT enzyme activity instead was increased in both. Fatty acids bound to phospholipids and serum cholesterol were mostly monounsaturated. Free fatty acid concentration was normal and they appeared mostly bound to the LDL and HDL3 fractions, which are increased in this disease and appear to replace albumin in one of its main carrier functions.
Galactose metabolism in transferase‐deficient galactosaemic and normal long‐term lymphoid cell lines
Authors: Beratis N. G. , Wilbur L. 
Published: June 2005

SummaryThe activity (mean±SD) of galactose‐1‐phosphate uridyl transferase in two long‐term lymphoid cell lines from Caucasian patients with transferase deficiency galactosaemia, a heterozygote, and eight normal subjects was 0, 78 and 168±55 nmol UDPG consumed (mg protein)−1h−1, respectively. Also, no activity was found in erythrocytes and cultured fibroblasts from the patients. A small number of cells of the galactosaemic lines cultured in medium, in which galactose was substituted for glucose, survived for 37 days. Normal and galactosaemic lines incubated withD‐galactose‐[1‐14C] liberated 218.2±65.6 and 18.1 pmol14CO2 (mg cellular protein)−1 (6h)−1, respectively. The evolution of14CO2 fromD‐glucose‐[1‐14C] was similar in normal and galactosaemic lines. In the presence of [3H] galactose the radioactivity incorporated into TCA‐precipitated material of the galactosaemic lines was 6.8% of the normal lines. Approximately 26% and 1.3% of the total radioactivity was incorporated into molecular species with a molecular weight greater than 400000 daltons in normal and galactosaemic cells, respectively. Similar molecules were identified in the cell‐free medium of both normal and deficient cells except for an 18000 daltons molecule identified only in the medium of the normal cells. These findings indicate that a small amount of galactose is metabolized in galactosaemic lines with no transferase activity.
Intermittent hypermethioninaemia associated with normal hepatic methionine adenosyltransferase activity: Report of a case
Authors: Jhaveri B. M. , Buist N. R. M. , Gaull G. E. , Tallan H. H. 
Published: June 2005

AbstractA 5‐month‐old infant was found to have hypermethioninaemia (0.8 µmol/ml) that has persisted intermittently (0.02–1.3 µmol/ml) over a period of 3 years. She presented with developmental delay and failure to thrive associated with gross abuse and neglect. Histological examination of the liver revealed inflammation of the portal triads. The activity of hepaticl‐methionine‐S‐adenosyltransferase (EC 2.5.1.6) was normal. Whether the biochemical findings were the cause or the result of the hepatic damage is uncertain, but the minimal histological findings in the liver suggest a primary biochemical defect.
Isovaleric acidaemia presenting with dwarfism, cataract and congenital abnormalities
Authors: Duran M. , Bruinvis L. , Ketting D. , Wadman S. K. , van Pelt B. C. , Batenburg‐Plenter A. M. 
Published: June 2005

AbstractIsovaleric acidaemia was diagnosed in a 9‐year‐old girl with an unusual clinical presentation. She was severely mentally retarded, had an extreme growth retardation, bilateral cataracts, multiple fractures of the long bones, vitium cordis and malformations of the head. Frequent infections occurred since early childhood. The relevance of these findings is discussed.
Allopurinol challenge test in children
Authors: Burlina A. B. , Ferrari V. , Dionisi‐Vici C. , Bordugo A. , Zacchello F. , Tuchman M. 
Published: June 2005

SummaryThe allopurinol challenge test was performed on 44 healthy subjects (28 children and 16 adolescents) in order to establish normal values of urinary orotic acid excretion following allopurinol ingestion in the paediatric population. The subjects were divided into three groups according to their age: 6 months to 6 years; 6 years to 10 years; and 10 years to 17 years. They were given 100 mg, 200 mg, or 300 mg of allopurinol, respectively (based on age) in a single oral dose. Maximum peak urinary orotic acid levels following ingestion of allopurinol were 13.0 (n=14), 9.3 (n=14), and 10.2 (n=16) µmol/mmol creatinine in the three groups, respectively. In all children tested the peak orotic acid level was 3.1±2.7 µmol/mmol creatinine (mean ± SD,n=44). This allopurinol challenge test was also performed in six children with ureacycle disorders, including five females with ornithine transcarbamylase (OTC) deficiency, all of whom demonstrated abnormally elevated levels of urinary orotic acid (peak levels of 26–134 µmol/mmol creatinine) following allopurinol ingestion.
Fructose and glucagon loading in siblings with fructose‐1,6‐diphosphatase deficiency in fed state
Authors: Nagai T. , Yokoyama T. , Hasegawa T. , Tsuchiya Y. , Matsuo N. 
Published: June 2005

SummaryHypoglycaemia induced by fructose administration is one of the diagnostic clues to fructose‐1,6‐diphosphatase (FDPase) deficiency (McKusick 229700). However, the pathological mechanism of this reactive hypoglycaemia is not fully known. This paper describes two siblings with FDPase deficiency, diagnosed enzymatically in leukocytes, who failed to correct reactive hypoglycaemia after glucagon administration even in the fed state, supporting a possibility that disturbed hepatic phosphorylase activity may be a main cause of reactive hypoglycaemia.
In vivo13C‐NMR evaluation of glycogen content in a patient with glycogen storage disease
Authors: Labrune Ph. , Jehenson Ph. , Syrota A. , Odièvre M. 
Published: June 2005

SummaryGlycogen storage disease was suspected in a 10‐month‐old boy. Initial technical problems did not permit the determination of the precise enzyme deficiency, and type VI glycogen storage disease was only diagnosed at the age of 2 years. In the mean time, natural abundance13C nuclear magnetic resonance evaluation of muscular and hepatic glycogen content indicated normal muscular glycogen and increased hepatic glycogen in our patient, a finding which strongly argued for the diagnosis of type VI glycogen storage disease. Even though the use of nuclear magnetic resonance might seem, in this situation, a somewhat circuitous means of reaching the diagnosis, it appears that nuclear magnetic resonance could provide a useful tool for a non‐invasive diagnosis of glycogen storage diseases.
Mevalonate kinase assay using DEAE‐cellulose column chromatography for first‐trimester prenatal diagnosis and complementation analysis in mevalonic aciduria
Authors: Hoffmann G. F. , Brendel S. U. , Scharfschwerdt S. R. , Shin Y. S. , Speidel I. M. , Gibson K. M. 
Published: June 2005

SummaryMevalonic aciduria due to mevalonate kinase deficiency, an inherited defect of cholesterol biosynthesis, has presented with clinical variability in 10 patients from 7 families. We sought to define a genetic basis for this heterogeneity by determining mevalonate kinase activity in fibroblast heterokaryons obtained by polyethylene glycol fusion. To this end we developed a DEAE‐cellulose (Cl−) column chromatography procedure for assessing mevalonate kinase in cell extracts that would allow multiple rapid analyses. Fusion of control fibroblasts with those from affected patients from six families with mevalonate kinase deficiency yielded 37% of the mean control activity. None of the fusions between the six cell lines of patients resulted in measurable mevalonate kinase activity. Using the chromatographic procedure, we developed an optimized assay for mevalonate kinase in biopsied chorionic villi.Km values for chorionic villi were similar to those obtained in fibroblasts. Mevalonate kinase activity in biopsied chorionic villi showed a linear increase (0.75–4.3 nmol/min per mg protein) with gestational age from 7 to 14 weeks. Using the optimized assay in biopsied chorionic villi we performed a first‐trimester prenatal diagnosis in a pregnancy at risk for mevalonate kinase deficiency and correctly diagnosed an unaffected fetus. The availability of an optimized assay for mevalonate kinase in biopsied chorionic villi should allow reliable first‐trimester prenatal diagnosis for families at risk.