bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated plasma carnitine in the hepatic form of carnitine palmitoyltransferase‐1 deficiency
Authors: Stanley C. A. , Sunaryo F. , Hale D. E. , Bonnefont J. ‐P. , Demaugre F. , Saudubray J. ‐M. 
Published: June 2005

SummaryIn a boy with a defect in fatty acid oxidation due to the hepatic form of carnitine palmitoyltransferase‐1 deficiency, plasma carnitine concentrations were found to be twice normal. The elevation in plasma carnitine levels was accompanied by an unusually high renal threshold for free carnitine, suggesting a secondary increase in carnitine transport. Similar to other fatty acid oxidation disorders involving the carnitine cycle, urinary dicarboxylic acids were not abnormally elevated during illnesses. The combination of elevated plasma carnitine levels and absence of dicarboxylic aciduria may help to distinguish the hepatic form of carnitine palmitoyltransferase‐1 deficiency from other defects in fatty acid oxidation.
N‐acetylaspartic aciduria due to aspartoacylase deficiency — a new aetiology of childhood leukodystrophy
Authors: Hagenfeldt L. , Bollgren I. , Venizelos N. 
Published: June 2005

AbstractWe describe a male infant with psychomotor retardation and leukodystrophy who excretes large quantities ofN‐acetylaspartate in his urine. A high CSF/plasma concentration ratio ofN‐acetylaspartate indicates that this substance originates in the brain. Fibroblasts from the patient are deficient in aspartoacylase activity. It is proposed that the dysmyelination in the patient may be due to failure ofN‐acetylaspartate to serve as a carrier of acetyl groups from mitochondria to the cytosol for lipogenesis.
Adenine phosphoribosyltransferase deficiency: a case diagnosed by GC‐MS identification of 2,8‐dihydroxyadenine in urinary crystals
Authors: Christensen E. , Brandt N. J. , Laxdal T. 
Published: June 2005

AbstractLight microscopy of the urinary sediment from a child suffering from urinary tract disease showed massive crystalluria. Most of the sediment consisted of characteristic round and brownish crystals. 2,8‐Dihydroxyadenine was identified in the crystals by means of gas chromatography‐mass spectrometry. The diagnosis of adenine phosphoribosyltransferase deficiency was established by the finding of a very low activity of this enzyme in erythrocytes from the patient, and of half the normal activity in the parents.The patient was first treated with a diet low in purine and with a high liquid intake. She stayed symptomless on this regimen, but the crystalluria persisted. On low doses of allopurinol the crystalluria disappeared.
Characterization of α‐mannosidase in feline mannosidosis
Authors: Raghavan S. , Stuer G. , Riviere L. , Alroy J. , Kolodny E. H. 
Published: June 2005

AbstractAcidic α‐mannosidase deficiency has been identified in a family of Blue Persian cats. Characterization of the residual activity revealed that theKm for the substrate, 4‐methylumbelliferyl‐α‐d‐mannoside, increased approximately three‐fold with a severe deficiency inVmax (1–2%) in homogenates of liver and brain of affected cats compared with controls. The residual activity at pH 4.0 in liver homogenates from affected cats is very thermolabile at 51°C while the control activity is stable at this temperature for 1h. Subcellular fractionation of liver was performed from a control and diseased cat in order to compare the properties of the different α‐mannosidases localized in these fractions. The residual activity present in the lysosomal fraction from diseased cat liver showed altered pH optimum, two‐fold increase inKm with a severely reducedVmax and increased thermolability compared with the activity in the lysosomal fraction from control liver. The thermal inactivation pattern andKm of the residual activity in the lysosomal fraction is different from the non‐lysosomal α‐mannosidase in the liver of the affected cat. This suggests that the residual activity in the lysosomal fraction of the liver from the affected cat is not due to contamination of non‐lysosomal α‐mannosidase in this fraction. Whether this residual activity represents the properties of the mutant enzyme or yet another minor normal component of lysosomes different from the major inactive mutant or absent lysosomal enzyme remains to be elucidated.
Newborn urine screening experience with over one million infants in the Quebec Network of Genetic Medicine
Authors: Lemieux B. , Auray‐Blais C. , Giguère R. , Shapcott D. , Scriver C. R. 
Published: June 2005

SummaryWe screened urine for chemical individuality in over 1 million newborn infants, by various chromatographic (thin‐layer), chemical and spectrophotometric methods, 12 procedures in all. The programme is part of the Quebec Network of Genetic Medicine. Voluntary urine screening began in 1971 and has evolved with changes in choice of tests and times of sample collection. Urine samples were collected on filter paper at either 5, 14 or 21 days after birth; results were best with the 21‐day test. Compliance is over 94% with the latter and over 98% with requests for repeat samples. Screening is centralized in one laboratory; follow‐up diagnosis, counselling and management are done at four regional centres. Incidence of phenotypes ranged from 1:4300 live births (for expressed cystinuria alleles) to 1 per million (for hyperargininaemia). Over 20 inherited Mendelian disorders were identified. 30 patients required aggressive medical management. We show how this programme can be used for neuroblastoma screening.
Biochemical genetics of HPRTCapeTown: is the defect in the HPRT gene?
Authors: Galloon T. , Harley E. H. 
Published: June 2005

SummaryHPRTCapeTown shows low levels of purine salvage in cultured cells which is associated with the unusual property of substrate inhibition by its purine substrates in erythrocyte haemolysates. Since it is not certain that the defect is in the HPRT gene, we studied enzyme kinetics in cell‐free preparations of erythrocytes and transformed lymphoblasts from both the proband and his obligate heterozygote daughter and studied purine salvage in intact cells. Substrate inhibition was demonstrated in erythrocyte and lymphoblast cell‐free extracts from the proband and his daughter and lymphoblasts from the daughter showed similar growth properties in selective media to her father. These results were all consistent with the defect being in the HPRT gene.
Lesch‐nyhan syndrome: Growth delay, testicular atrophy and a partial failure of the 11β‐hydroxylation of steroids
Authors: Watts R. W. E. , Harkness R. A. , Spellacy E. , Taylor N. F. 
Published: June 2005

SummaryThere is a failure of growth in hypoxanthine guanine phosphoribosyltransferase deficiency; slow weight gain is marked after the second year of age but is apparent in the birth weights of all eight of our patients for whom we have data. However, head growth and bone development are less affected than weight.A partial defect in the adrenocortical 11β‐hydroxylation of steroids was demonstrated after ACTH stimulation in all four patients studied. This hydroxylation takes place in mitochondria the function of which is modulated by purine nucleotide concentrations; this may be the link with the enzyme defect.Testicular atrophy at autopsy was found in two pubertal age boys and seven patients aged 12–17 years had no signs of puberty. All five boys aged 3–11 years showed less than the normal mean response of plasma testosterone concentration to human chorionic gonadotrophin despite the normal histological appearance of the testes of one 6‐year‐old‐boy. Follicle stimulating hormone responses to gonadotrophin releasing hormone are probably less than in normal in at least three of the seven prepubertal boys. The absence of the normally high activities of hypoxanthine guanine phosphoribosyltransferase in testes appears to inhibit their ability to respond to gonadotrophin.
Acid β‐mannosidase of human plasma: Influence of age and sex on enzyme activity
Authors: Cooper A. , Hatton C. , Sardharwalla I. B. 
Published: June 2005

SummaryOptimum conditions for assay of human plasma β‐mannosidase activity were determined. Maximum activity was observed at pH 3.0–3.4, the apparentKm was 0.9 mmol L−1 and enzymatic hydrolysis was linear for at least 60 min. Assays were performed on plasma from two siblings with the recently described condition β‐mannosidosis and their parents and controls. Both β‐mannosidosis patients showed a marked deficiency of β‐mannosidase activity. Control samples showed no variation between sexes (p>0.05) but enzyme activity varied significantly with age (p<0.05). Highest activity was observed in the 0–1 year age group, activity then decreasing to adulthood, Both mother and father of the affected individuals showed reduced activity (34% and 53%, respectively) compared to age‐matched controls. This suggests that heterozygote detection in this condition is possible using plasma, provided the variation of activity with age is taken into consideration.
Impaired glucose transport in polymorphonuclear leukocytes in glycogen storage disease Ib
Authors: Bashan N. , Potashnik R. , Hagay Y. , Moses S. W. 
Published: June 2005

SummaryA study of 2‐deoxyglucose transport into polymorphonuclear leukocytes (PMN) was performed in three patients with glycogen storage disease (GSD) type Ib. The rate of 2‐deoxyglucose transport into GSD Ib PMN was 30% of that of cells of normal controls. In GSD Ib lymphocytes, transport was normal.Km for 2‐deoxyglucose in the PMN of one patient was within the normal range.The reduced transport was not due to the elevation in Km for 2‐deoxyglucose nor to the decreased rate of phosphorylation of 2‐deoxyglucose. The striking limitation of glucose transport across the cell membrane may account for the impairment of leukocyte function which is characteristic of GSD Ib.
Prevalence of different types of lysosomal storage diseases in saudi arabia
Authors: Ozand P. T. , Gascon G. , Al Aqeel A. , Roberts G. , Dhalla M. , Subramanyam S. B. 
Published: June 2005

SummaryThe frequency of different types of lysosomal storage diseases in 125 referred cases, collected over three years, was compared to the occurrence elsewhere. The data suggest that mucopolysaccharidosis (MPS) type IVA (Morquio disease), multiple sulphatase deficiency, Niemann‐Pick disease type B, GM2 gangliosidosis type ‘0’ (Sandhoff disease), and ceroid lipofuscinosis (Jansky‐Bielschowsky and Batten‐Spielmeyer‐Vogt syndromes) are encountered frequently in Saudi Arabia, as compared to other storage diseases. In contrast, some other diseases such as the adult variant of Gaucher's disease were not observed. Half of the GM2 gangliosidosis type ‘0’ cases originated from one large tribe in the country. Other conditions did not show tribal predilection. The ceroid lipofuscinosis cases in Saudi Arabia originated from four large families. Consanguineous marriages taking place within tribal boundaries probably account for the pattern observed.
β‐Mannosidase deficiency: Heterogeneous manifestation in the first female patient and her brother
Authors: Kleijer W. J. , Hu P. , Thoomes R. , Boer M. , Huijmans J. G. M. , Blom W. , Van Diggelen O. P. , Seemanova E. , Macek M. 
Published: June 2005

Summaryβ‐Mannosidase deficiency was demonstrated in fibroblasts of a girl who showed severe psychomotor retardation, bone deformities and gargoylism and recurrent skin and respiratory infections and who died at 20 years of age from bronchopneumonia. This first demonstration of a female patient confirms the autosomal recessive inheritance of β‐mannosidosis. Further investigation of this gipsy family revealed β‐mannosidosis in an older brother with a milder manifestation of gargoyl facial dysmorphology, mental retardation, hearing impairment and recurrent infections. β‐Mannosidase activity was completely deficient in his cultured skin fibroblasts, leukocytes and plasma. In urine a characteristic disaccharide was present. Heterozygote levels of β‐mannosidase were found in fibroblasts and/or plasma of the parents and one sister.
Restriction fragment length polymorphisms among Japanese detected with a dihydropteridine reductase cDNA gene probe
Authors: Hayasaka K. , Narisawa K. , Ohura T. , Ogawa E. , Dahl H. ‐H. M. 
Published: June 2005

SummaryUsing a human dihydropteridine reductase (DHPR) cDNA, the frequency of restriction fragment length polymorphisms (RFLPs) with restriction endonucleases AvaII, MspI, NcoI and HinfI was estimated in unrelated, unaffected Japanese. The allele frequencies are different from those found in Caucasians, especially with MspI and HinfI. However, approximately 60% of Japanese are heterozygous for at least one of the RFLPs and analysis of one family with DHPR deficiency was shown to be informative. RFLP linkage analysis will be useful in the Japanese population as previously reported for Caucasians.
Prenatal exclusion of ornithine transcarbamylase (OTC) by using RFLP analysis
Authors: Liechti S. , Dionisi Vici C. , Bachmann C. , Mazziotta M. R. M. , Bartuli A. , Sabetta G. 
Published: June 2005

SummaryThe use of restriction fragment length polymorphism studies for prenatal exclusion of OTC deficiency in a carrier mother is reported.
X‐linked pyruvate dehydrogenase E1α subunit deficiency in heterozygous females: Variable manifestation of the same mutation
Authors: Dahl H‐H. M. , Hansen L. L. , Brown R. M. , Danks D. M. , Rogers J. G. , Brown G. K. 
Published: June 2005

SummaryThree female patients are described with pyruvate dehydrogenase (PDH) deficiency as a result of mutation in the X‐linked gene for the E1α subunit of the complex. Two of these patients illustrate typical presentations of PDH E1α deficiency, with severe neurological dysfunction, degenerative changes and developmental anomalies in the brain, together with variable lactic acidosis. The third patient extends the known spectrum of the condition to include mild to moderate mental retardation and seizures in an adult. All three patients have the same mutation in the PDH E1α gene. This mutation, a C‐to‐T substitution in a CpG dinucleotide in amino acid codon 302 (designated R302C), results in the replacement of arginine by cysteine at this position. The mildly affected adult was the mother of one of the other patients, making this the first described instance of mother‐to‐daughter transmission of a mutation causing PDH E1α deficiency. The genetic basis of the variable expression of X‐linked PDH E1α deficiency in heterozygous females is discussed.
Mutation of E1α gene in a female patient with pyruvate dehydrogenase deficiency due to rapid degradation of E1 protein
Authors: Ito M. , Huq A. H. M. M. , Naito E. , Saijo T. , Takeda E. , Kuroda Y. 
Published: June 2005

SummaryA mutation of an insertion of 4 bp in the gene for the α subunit of pyruvate dehydrogenase (E1α) was found in a female with pyruvate dehydrogenase deficiency due to the rapid degradation of α and β subunit proteins of pyruvate dehydrogenase. This mutation caused a frameshift that altered the amino acid sequence and created a premature stop codon. This 4‐bp insertion has been found in an unrelated female patient with E1α deficiency. It is rare that the same mutation is found in unrelated patients with this rare inborn error of metabolism. Furthermore, short deletions or duplications in the E1α gene of patients with E1α deficiency have been found only in exons 10 and 11. These exons may be hot spots for the mutations by the recombinational processes. This patient was heterozygous for the normal and a mutant allele. However, in most of the cultured skin fibroblasts from this patient, the mutant allele was expressed. These observations suggest that the X chromosome containing the normal allele was predominantly inactivated so that she developed lactic acidaemia and neurological abnormalities despite being heterozygous. The mutant α subunit protein failed to form a stable structure of pyruvate dehydrogenase, so that both α and β subunit proteins were degraded rapidly.
Hypertrophic obstructive cardiomyopathy in a neonate with the carbohydrate‐deficient glycoprotein syndrome
Authors: Clayton P. T. , Winchester B. G. , Keir G. 
Published: June 2005

SummaryThe carbohydrate‐deficient glycoprotein (CDG) syndrome in its most severe form (neonatal olivopontocerebellar atrophy) is a life‐threatening multisystem disease. We report a neonate who was referred for cardiological assessment because of respiratory distress, a murmur and episodes of desaturation. After initial spontaneous improvement he presented at 9 weeks with evidence of a severe hypertrophic obstructive cardiomyopathy (HOCM). The diagnosis of CDG syndrome was suggested by the characteristic dysmorphic features, hypotonia, visual inattention and severe failure to thrive; it was confirmed by electrophoresis of serum transferrin. HOCM can be a feature of the CDG syndrome, in addition to the (previously reported) pericardial effusions.
Isolated biotin‐resistant deficiency of 3‐methylcrotonyl‐CoA carboxylase presenting as a clinically severe form in a newborn with fatal outcome
Authors: Bannwart C. , Wermuth B. , Baumgartner R. , Suormala T. , Wiesmann U. N. 
Published: June 2005

SummaryThe son of Kurdish, consanguineous parents (cousin marriage) presented from the first day of life with inititally focal and later generalized attacks of epileptic seizures and a severe generalized muscular hypotonia. Urinary excretion of 3‐hydroxyisovalerate and of 3‐methylcrotonylglycine was persistently increased. Diagnosis of isolated biotin‐resistant 3‐methylcrotonyl‐CoA carboxylase deficiency was confirmed in cultured fibroblasts. Psychomotor retardation was progressive, seizures and marked EEG abnormalities persisted. Treatment with leucine and protein‐resistricted diet under hospital control did not significantly improve these conditions. The patient died from a cardiac and circulatory failure after a prolonged epileptic attack, with bronchial aspiration. The non‐responsiveness of our patient to therapy and the fatal outcome indicate the existence of a severe neonatal variant of this otherwise rather benign genetic enzyme deficiency.
Differential diagnosis of hydroxydicarboxylic aciduria based on release of3H2O from [9,10‐3H]myristic and [9,10‐3H]palmitic acids by intact cultured fibroblasts
Authors: Olpin S. E. , Manning N. J. , Carpenter K. , Middleton B. , Pollitt R. J. 
Published: June 2005

SummaryIntact cultured fibroblasts from patients with deficiency of long‐chain 3‐hydroxyacyl‐CoA dehydrogenase release3H2O from [9,10‐3H]myristic acid and [9,10‐3H]palmitic acid more slowly than normal. The ratio of activity (palmitate/myristate) is also low and the expression (rate with palmitate)2/(rate with myristate) gives good differentiation between affected and unaffected cells. In some patients who have shown hydroxydicarboxylic aciduria when unwell there is reduced3H2O production from [9,10‐3H]myristic and [9,10‐3H]palmitic acids by intact cultured fibroblasts but normal 3‐hydroxyacyl‐CoA dehydrogenase activities in disrupted cells. The palmitate/myristate ratio is higher than in long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency. The basic defect in these patients is still unknown but it is suggested that caution be used over the administration of medium‐chain triglyceride.
Bone marrow transplantation for Niemann‐Pick Type IA disease
Authors: Bayever E. , Kamani N. , Ferreira P. , Machin G. A. , Yudkoff M. , Conard K. , Palmieri M. , Radcliffe J. , Wenger D. A. , August C. S. 
Published: June 2005

SummaryBone marrow transplantation has been undertaken with encouraging results as therapy for a wide variety of lysosomal storage diseases. We report a case of Niemann‐Pick disease Type IA in which, despite the presence of only mild hypotonia with depressed reflexes, the clinical course of the disease appeared to be only slightly modified by this procedure, which was performed at the earliest practical opportunity. The patient was diagnosed early when asymptomatic, because of a family history of an affected sibling who died at 14 months. He received a bone marrow transplant from an HLA‐identical, MLC non‐reactive sibling donor, whose leukocyte sphingomyelinase activity was in the homozygote normal range. There was adequate engraftment as evidenced by persistently normal leukocyte sphingomyelinase activities, and there was no evidence of graft‐versus‐host disease. Visceral storage and neurological impairment were less rapidly progressive than in his untreated sibling but he eventually died at 30 months. Autopsy confirmed that this was essentially due to the effects of the underlying Niemann‐Pick disease. We conclude that despite some success in other neurovisceral lysosomal storage disorders, bone marrow transplantation is not likely to be an adequate treatment for Niemann‐Pick disease Type IA.
3β‐hydroxy‐Δ5‐C27‐steroid dehydrogenase deficiency; effect of chenodeoxycholic acid therapy on liver histology
Authors: Horslen S. P. , Lawson A. M. , Malone M. , Clayton P. T. 
Published: June 2005

SummaryThe second step in the pathway for synthesis of bile acids from cholesterol is catalysed by the enzyme 3β‐hydroxy‐Δ5‐C27‐steroid dehydrogenase. Deficiency of this enzyme has been reported to produce cholestatic liver disease with progressive cirrhosis. Treatment with chenodeoxycholic acid led to clinical and biochemical improvement in one patient. We report a further child with this disorder who presented with prolonged neonatal jaundice followed by symptoms of malabsorption of fat‐soluble vitamins. Bile acid replacement therapy resulted in clinical and biochemical improvement; it was also possible to demonstrate improvement in the histological appearance of the liver biopsy 4 months after commencing treatment.
Storage material from urine and tissues in the nephropathic phenotype of infantile sialic acid storage disease
Authors: Paschke E. , Gruber W. , Ring E. , Sperl W. 
Published: June 2005

SummaryWe analysed urine and tissue specimens from two nephrotic infantile sialic acid storage disease patients (nISSD) for free and bound sialic acids in comparison to non‐nephrotic ISSD patients (ISSD), patients with minimal change nephrosis (nControl) and normal controls (Control). No differences in the excretion of urinary free sialic acid could be detected between ISSD and nISSD urines. Sialyloligosaccharide fractions were only slightly elevated and of apparently normal composition. Owing to glomerular dysfunction, measurable quantities of protein‐bound sialic acids were present in nISSD and nControl.In nISSD tissues, free sialic acid was elevated 18–100‐fold above control and 3–12‐fold above Niemann‐Pick A (NPA) samples. The storage of membrane‐bound sialic acid was slightly increased compared to control tissues, but equal to those from NPA, thus reflecting an unspecific increase of membranes due to lysosomal storage.According to these results no major biochemical differences were detectable between ISSD and nISSD. The nephrotic syndrome in nISSD could not be related to a general deficit in the sialylation of glycoproteins. Nevertheless, a cell membrane‐specific alteration in sialoglycoproteins of glomerular cells might still be possible.