bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylase b kinase deficiency in man: a review
Authors: van den Berg I. E. T. , Berger R. 
Published: June 2005

SummaryPhosphorylase b kinase is involved in the activation of glycogen phosphorylase and is thus involved in the breakdown of glycogen. The enzyme exists as several tissue specific isoenzymes of which the muscle enzyme (rabbit) has been most characterized. It is a multimeric protein composed of four subunits, α, β, γ and δ. The four subunits are coded on different chromosomes, the α, β and γ subunit genes being on the X, 16 and 17 chromsomes respectively. The δ subunit is a calmodulin and confers calcium sensitivity on phosphorylase b kinase. Tissue specificity of the enzyme is conferred, at least in some cases, by variation in the γ subunit.Seven different clinical types of phosphorylase b kinase deficiency have been described. The most common type is X‐linked and affects the liver only; other types affect liver, muscle and liver, muscle or heart and have an autosomal recessive mode of inheritance, while in some types the mode of inheritance is not clear. Diagnosis based on the study of erythrocytes or leukocytes can be misleading due to the tissue specific nature of the enzyme, and liver or muscle biopsies may be required.
A preliminary report of the collaborative study of maternal phenylketonuria in the United States and Canada
Authors: Koch R. , Hanley W. , Levy H. , Matalon R. , Rouse B. , Cruz F. Dela , Azen C. , Friedman E. Gross 
Published: June 2005

SummaryThe Maternal Phenylketonuria Collaborative Study (MPKUCS), encompassing all the United States and provinces of Canada, is a prospective, longitudinal investigation designed to ascertain the efficacy of phenylalanine‐restricted therapy in protecting the fetus from high maternal phenylalanine concentrations in women with hyperphenylalaninaemia.Preliminary findings are reported for 147 pregnancies for whom the recommended therapeutic range of blood phenylalanine was 120–360 µmol/L. Sixty‐three pregnancies had complete data for analysis. Dietary control was attempted prior to conception in 10 out of 63 women. Significant negative correlations were noted in length, weight and head circumference and blood phenylalanine concentrations during pregnancy. Average reported phenylalanine levels by trimester for 63 hyperphenylalaninaemic pregnancies resulting in live births revealed that no group requiring treatment achieved levels below 360 µmol/L until the third trimester. Median birth measurement percentiles revealed that all groups studied generally had smaller head size compared with birth length and weight. Those started on diet after the first trimester achieved a head circumference below the 10th percentile.The implication of small head circumference for subsequent intellectual development is unclear at this time. Furthermore, the study must evaluate more offspring of women having optimal preconception and pregnancy restriction of phenylalanine.
A retrospective study of a patient with homozygous form of acute intermittent porphyria
Authors: Beukeveld G. J. J. , Wolthers B. G. , Nordmann Y. , Deybach J. C. , Grandchamp B. , Wadman S. K. 
Published: June 2005

SummaryIn 1964 a child with an exceptional form of porphyria was described; she excreted persistently excessive amounts of delta‐aminolaevulinic acid, porphobilinogen and uroporphyrin in her urine from early childhood. The biochemical profile resembled that of acute intermittent porphyria (AIP). The child died at the age of 8 years. Reinvestigation of some urine samples by HPLC revealed differences in comparison with urines of other patients with AIP. The clinical picture characterized by porencephaly and severe retardation in development was completely different from that of AIP. Her mother suffered from AIP but the father never had attacks. Investigations on blood and urine samples of the father showed that he also was affected. Due to the early onset in the index patient, its persistent character, and the fact that both parents are affected we postulate retrospectively to have diagnosed a case of homozygous or a double heterozygous AIP, hitherto undescribed.
Impaired sulphated glycosaminoglycan metabolism in a patient with GM‐2 gangliosidosis (Tay‐Sachs disease)
Authors: Toma L. , Pinto W. , Rodrigues V. C. , Dietrich C. P. , Nader H. B. 
Published: June 2005

SummaryAn abnormal urinary excretion of sulphated glycosaminoglycans in a patient with GM‐2 gangliosidosis (Tay‐Sachs disease) is described. Besides the accumulation of GM‐2 ganglioside in liver and lack of hexosaminidase A, the patient shows an abnormal urinary excretion of an iduronic acid‐rich low molecular weight heparan sulphate. Also, no dermatan sulphate could be detected in the urine, whereas this compound was the main sulphated glycosaminoglycan in the liver of the patient. Heparan sulphate was the main glycosaminoglycan of normal liver. The total amount of sulphated glycosaminoglycans in the urine and liver of the patient did not differ significantly from the amounts found in the liver and urine of normal subjects. Several plasma glycosidases have been assayed and the activities did not differ significantly from the values obtained for the plasma of normal subjects.
Structure and function of the mitochondrial genome
Authors: Clayton D. A. 
Published: June 2005

SummaryIt is now clear that molecular defects in human mitochondrial DNA play a significant role in human disease. Mitochondrial DNA mutations range from single base changes in the 16.5 kilobase‐pair genome up to large deletions and rearrangements. Independently of the actual cause of a given mutation, it is possible to predict at least some of the consequences of changes in mitochondrial DNA sequence. This paper reviews our overall understanding of the mode and mechanism of mitochondrial DNA replication and transcription and how this relates to mitochondrial gene expression. This provides a background to anticipate the nature and extent of mitochondrial DNA sequence changes that might be of physiological consequence.
Abnormalities of human sex determination
Authors: Ferguson‐Smith M. A. 
Published: June 2005

SummaryCytogenetic and molecular studies in patients with abnormalities of sex determination have been the key to the isolation and investigation of candidates for the primary testis determining factor (TDF). A gene, SRY, isolated from the sex determining region of the Y chromosome within 5 kilobases of the pairing segment boundary, has been characterized recently which fulfils the expectations of TDF. It is expressed in the embryonic gonads at the critical time of differentiation; it is highly conserved among mammals; it has the structure of a transcription regulator; and mutations within its conserved domain are found in 10% of sex‐reversed XY females. The murine homologue of this gene has been shown to cause sex reversal in XX embryos following injection of a 14 kb DNA fragment containing SRY into fertilized eggs. However, most XX true hermaphrodites and a proportion of XX sex‐reversed males lack SRY despite the presence of testicular differentiation. It is postulated that the constitutive activation of an X‐linked gene, TDF‐2, normally regulated by SRY, is responsible for male differentiation in these cases. The female phenotype of XY individuals with duplications of Xp may be the result or deletion of disruption of TDF‐2.
Prenatal diagnosis of Hurler disease by analysis of α‐iduronidase in chorionic villi
Authors: Young E. P. 
Published: June 2005

SummaryTwenty‐four pregnancies at risk for Hurler disease (MPS I) were monitored by measurement of α‐iduronidase in chorionic villi. Adequate samples were obtained for direct assay of the villi in 22 pregnancies. Five were found to be affected and the pregnancies were terminated. In another pregnancy an equivocal result was obtained on direct assay but analysis of the cultured chorionic cells showed the fetus to be affected. In one pregnancy where an exceptionally small biopsy was obtained, direct assay indicated the fetus to be unaffected. Following amniocentesis this result was shown to be incorrect. These results confirm that, provided an adequate sample is obtained, an accurate diagnosis can be made by direct assay of chorionic villi in pregnancies at risk for Hurler disease.
Prospective versus clinical diagnosis and therapy of acute neonatal hyperammonaemia in two sisters with carbamyl phosphate synthetase deficiency
Authors: Tuchman M. , Mauer S. M. , Holzknecht R. A. , Summar M. L. , Vnencak‐Jones C. L. 
Published: June 2005

SummaryTwo female siblings were treated for acute neonatal hyperammonaemia due to complete carbamyl phosphate synthetase I deficiency. The first child was detected clinically at 65 hours of age and therapy started at 79 hours. The second child was followed from birth and therapy started at 5 hours of age. The extrapolated rate of increase of blood ammonia, in the first hours of life before therapy started, was 19 µmol L−1 h−1 in both babies. Peak blood ammonia level was 2235 µmol/L in the first (clinically detected) child and 271 µmol/L in the second (prospectively followed) child. The second child became symptomatic at 3 hours of age when blood ammonia level was as low as 90 µmol/L, whereas blood ammonia levels above 100 µmol/L caused no symptoms during recovery. The child detected clinically required haemodialysis and peritoneal dialysis to treat the hyperammonaemia. In the prospectively treated child, early therapy with intravenous sodium benzoate and sodium phenylacetate slowed the rate of increase in blood ammonia level, but this therapy did not prevent the need for peritoneal dialysis.
Neuropathological and clinical correlations in hurler disease
Authors: Watts R. W. E. , Spellacy E. , Hume Adams J. 
Published: June 2005

AbstractWe report studies on two patients (1 and 2) with Hurler disease. They both had all of the non‐neurological features of Hurler disease to a similar and extreme degree and similar signs of brain damage on computed tomography. However, intellectual function was unusually well‐preserved in patient 1, but seriously and typically impaired in patient 2. The reason for this discrepancy has been investigated by reference to the neuropathological findings, the results of α‐l‐iduronidase assays using different substrates and comparisons to other cases (patients 3 and 4). We suggest that patient 1 is an unusual variant of the disease who may have had a very low residual α‐l‐iduronidase activity in neuronal cells only, and that this could not be demonstrated by either enzyme assays on whole brain using the 4‐methylumbelliferyliduronide substrate (Crowet al., 1983) or in studies on fibroblast lysates using a radioactive disaccharide substrate.
Incidence of disorders tested by systematic screening: Confidence limits and comparison of programmes
Authors: Bachmann C. , Colombo J. ‐P. 
Published: June 2005

AbstractUsing the data from screening done in Switzerland since 1965, we showed that the probability of finding cases with increased phenylalanine or leucine concentrations is compatible with a Poisson distribution. If there are no trends present from year to year and if the Poisson distribution is an accurate fit further statistical treatment is possible. The advantage of using the Poisson distribution is exemplified by the calculation of confidence limits for the incidence of hyperphenylalaninaemia, maple syrup urine disease and hypothyroidism. Furthermore, statistical comparisons between different screening programs are easily done.
Pregnancy and argininosuccinic aciduria
Authors: Worthington S. , Christodoulou J. , Wilcken B. , Peat B. 
Published: June 2005

SummaryWe present the outcome of a pregnancy in a woman with mild argininosuccinic lyase deficiency to add to the collective experience of the maternal and fetal effects of urea cycle defects. In females affected with argininosuccinic lyase deficiency, careful clinical and biochemical monitoring of pregnancy will minimize the risk of metabolic decompensation in the perinatal period. Furthermore, it would appear that argininosuccinate is not teratogenic to the development of the human fetus.
Major hyperpipecolataemia in a normal adult
Authors: Vallat C. , Denis S. , Bellet H. , Jakobs C. , Wanders R. J. A. , Mion H. 
Published: June 2005

SummaryWe describe the fortuitous discovery of a 44‐year‐old man with a very high hyperpipecolataemia (250 µmol/L; normal <2.5). This patient has none of the clinical features seen in peroxisomal diseases, he is a strictly normal intelligent adult. A stereochemical study of this pipecolic acid was performed usingd‐amino acid oxidase, and identified it asl‐pipecolic acid. We suggest that isolatedl‐hyperpipecolataemia may be a benign trait.
First trimester prenatal diagnosis of metachromatic leukodystrophy on chorionic villi by ‘Immunoprecipitation—electrophoresis’
Authors: Poenaru L. , Castelnau L. , Besançon A‐M. , Nicolesco H. , Akli S. , Theophil D. 
Published: June 2005

SummaryPrenatal diagnosis of metachromatic leukodystrophy (MLD) due to arylsulphatase A (ASA) deficiency can be performed by amniocentesis with the disadvantage of a late pregnancy termination.Whether chorionic villi (CV) obtained by trophoblast biopsy during the first trimester of pregnancy can be useful for diagnosis depends on the reliability of results. The complexity of arylsulphatase expression in CV and the existence of several isozymes make diagnosis difficult. However, the use of an anti‐ASA antiserum enabled us to discriminate between ASA and a comigrating contaminant isozyme, and the antigen‐antibody (Ag‐Ab) complex gave better evidence of the presence or absence of ASA after enhancement of activity with 4‐methylumbelliferyl sulphate (4‐MUS).We propose that immunoprecipitation followed by electrophoresis could be a valuable method of MLD prenatal diagnosis on chorionic villi.
Prolidase deficiency: A patient without hydroxyproline‐containing iminodipeptides in urine
Authors: Wysocki S. J. , Hahnel R. , Mahoney T. , Wilson R. G. , Panegyres P. K. 
Published: June 2005

SummaryA 17‐year‐old girl was shown to have prolidase deficiency on the basis of the presence of large amounts of proline‐containing dipeptides in urine and an almost complete absence of prolidase in plasma and erythrocytes. Unlike most earlier cases of this genetic defect our patient did not excrete hydroxyproline‐containing dipeptides in her urine.
Pristanic acid does not accumulate in peroxisomal acyl‐CoA oxidase deficiency: Evidence for a Distinct peroxisomal pristanyl‐CoA oxidase
Authors: ten Brink H. J. , Poll‐The B. T. , Saudubray J. M. , Wanders R. J. A. , Jakobs C. 
Published: June 2005

SummaryThe concentration of pristanic acid was measured in plasma from a patient with an isolated peroxisomal very long chain fatty acid (VLCFA) acyl‐CoA oxidase deficiency, a defect in peroxisomalβ‐oxidation resulting in accumulation of VLCFA in plasma and tissues. Although peroxisomes are believed to be involved in pristanic acidβ‐oxidation, the pristanic acid level in the patient's plasma was within the control range. This finding provides evidence for the existence of a pristanyl‐CoA oxidase distinct from the specific trihydroxycholestanoyl‐CoA and VLCFA acyl‐CoA oxidases.
A comparative study of sialyloligosaccharides isolated from sialidosis and galactosialidosis urine
Authors: van Pelt J. , Kamerling J. P. , Bakker H. D. , Vliegenthart J. F. G. 
Published: June 2005

SummarySialic acid‐containing carbohydrates were isolated from sialidosis urine by a combination of gel‐filtration on Bio‐Gel P‐6 and medium‐pressure anion‐exchange chromatography on Mono Q. The Mono Q fractions were subjected to 500‐MHz1H‐NMR spectroscopy, sugar analysis and analytical HPLC on Lichrosorb‐NH2. These methods indicated the presence of variousN‐acetyllactosamine type sialyloligosaccharides differing from each other in branching pattern and sialic acid linkage types. Among the structures were fully and partially sialylated mono‐, di‐, tri‐ and tetra‐antennary compounds. A comparison with the results from galactosialidosis urine indicated that essentially the same carbohydrates were present in both urines, but that the relative amounts of the various sialyloligosaccharides differ to some extent. Sialidosis urinary oligosaccharides contained relatively more α2–6 linked sialic acid than oligosaccharides from galactosialidosis urine. It could be concluded that the additionalβ‐galactosidase deficiency in galactosialidosis did not influence the nature of the excreted material and that the sialidase deficiency determined completely the defective catabolism of glycoproteins in both sialidosis and galactosialidosis.
Biochemical characterization of patients and prenatal diagnosis of sialic acid storage disease for three families
Authors: Clements P. R. , Taylor J. A. , Hopwood J. J. 
Published: June 2005

SummaryModifications of the assay method of Aminoff (1961) for the determination of sialic acid levels in urine, amniotic fluid, cultured cell homogenates and tissue homogenates, which reduce the interference from proteins by precipitation and from interfering chromogens by second derivative spectroscopy are described.Biochemical profiles of patients from three families with different clinical forms of sialic acid storage disease were made using data obtained with the new method. A family with two patients with the clinically severe, early‐onset form is described, in which a 9‐fold elevation of sialic acid can be detected in the skin fibroblasts and a 12‐fold elevation in the urine. A patient from the second family is described with very severe clinical features and with 160‐fold and 16‐fold elevations of sialic acid in the urine and skin fibroblasts respectively. A patient from a third family is described with mild clinical features but with a 160‐fold and 6‐fold elevation of sialic acid in urine and skin fibroblasts respectively. The data obtained in this study are compared with data obtained in other laboratories on other patients.The method was used to assess the levels of sialic acid present in amniotic cells and chorionic villus cells obtained prenatally from pregnancies in each of the three families. In one case, in which amniotic cells were elevated in sialic acid and were vacuolated, the pregnancy was terminated. Follow‐up studies confirmed the diagnosis. Pregnancies from the other two families were assessed to be not affected.
A sibship with a mild variant of Zellweger syndrome
Authors: Barth P. G. , Schutgens R. B. H. , Wanders R. J. A. , Heymans H. S. A. , Moser A. E. , Moser H. W. , Bleeker‐Wagemakers E. M. , Jansonius‐Schultheiss K. , Derix M. , Nelck G. F. 
Published: June 2005

SummaryA mild variant of Zellweger (cerebro‐hepato‐renal) syndrome was diagnosed in male and female siblings aged 7 and 2 years. They had mild facial dysmorphia, moderate psychomotor retardation, tapetoretinal degeneration, sensorineural deafness and hepatomegaly. Ultrastructural examination of a liver biopsy in the younger patient revealed the absence of recognizable peroxisomes. In both patients plasma levels of pipecolic acid, phytanic acid, trihydroxycoprostanoic acid and dihydroxycoprostanoic acid were elevated. The very long chain fatty acid C26:0 and the C26:0/C22:0 fatty acid ratio were elevated in plasma, but less than in classical Zellweger syndrome. In cultured fibroblasts, deficient acyl‐CoA:dihydroxyacetone phosphate acyltransferase and increased concentrations of C26:0 as well as C26:1 very long chain fatty acids were found within the ranges previously established for patients with classical Zellweger syndrome. Particle‐bound catalase was absent in fibroblasts. Despite the relatively mild clinical expression the biochemical abnormalities found in these patients are the result of a general peroxisomal dysfunction similar to the changes in classical Zellweger syndrome.
Review: Normal and abnormal central nervous system GABA metabolism in childhood
Authors: Jaeken J. , Casaer P. , Haegele K. D. , Schechter P. J. 
Published: June 2005

SummaryThe metabolism and function of central nervous system GABA is briefly reviewed. Hereditary disorders of the GABA metabolism presenting in childhood are discussed with particular emphasis on the recently identified succinic semialdehyde dehydrogenase deficiency and GABA‐transaminase deficiency, and on diseases associated with low CSF GABA which await further unravelling. Low CSF GABA concentrations are not always associated with convulsions. A separate section is devoted to the CSF as a tool in the diagnosis of these disorders. Finally, we present a few diagnostic and therapeutic guidelines.
Variation of lysosomal enzyme activity with gestational age in chorionic villi
Authors: Fukuda M. , Tanaka A. , Isshiki G. 
Published: June 2005

SummaryThe activities of 14 lysosomal enzymes in chorionic villi at gestational ages of 6–12 weeks were assayed.Arylsulphatases A and B, α‐glucosidase and β‐glucuronidase activities increased with advancing gestational age. When compared with the activity in cultured amniotic fluid cells, arylsulphatase A, β‐galactosidase, α‐glucosidase, heparan N‐sulphatase, α‐l‐iduronidase, α‐mannosidase, neuraminidase and sphingomyelinase showed significant differences. All except β‐glucuronidase showed lower activity in chorionic villi than in cultured amniotic fluid cells. Prenatal diagnosis using chorionic villi was possible except for α‐l‐iduronidase.Storage at −20°C up to 42 days did not significantly affect activity. The results emphasize the importance of using fresh or frozen age‐matched control tissue for diagnosis.
Trace element excess in PKU diets?
Authors: Sievers E. , Oldigs H. ‐D. , Dörner K. , Schaub J. 
Published: June 2005

SummaryKnowledge of trace element requirements of infants with phenylketonuria (PKU) fed a semisynthetic diet is limited. Three infants with PKU detected early were studied longitudinally in classical balance studies for 72 h, under domestic conditions, at the ages of 2, 5, 8, 12 and 16 weeks. Iron, copper and manganese concentrations in the diet and faeces were determined by atomic absorption spectroscopy. The median concentrations in the diet (4.8 mg Fe/L, 1.7 mg Cu/L, 0.43 mg Mn/L) exceed those in human milk. This is mainly due to supplementation of the amino acid preparation used. The increased intake led to a significantly higher daily retention of Cu and Mn from the PKU‐diet fed, with a median of 0.17 mg Cu/kg and 6.4 µg Mn/kg body weight; the median retention of Fe was 0.24 mg Fe/kg. Our results confirmed the doubts about the suitability of the present trace element supplementation in formula for infants with PKU during the first four months of life.
Long‐term effects of bone marrow transplantation on lysosomal enzyme replacement in β‐glucuronidase‐deficient mice
Authors: Bou‐Gharios G. , Adams G. , Pace P. , Olsen I. 
Published: June 2005

SummaryThis study uses bone marrow transplantation (BMT) between congenic strains of mice as an experimental model to examine enzyme replacement therapy of lysosomal storage diseases. Bone marrow cells from donor mice which have normal levels of the lysosomal enzyme β‐glucuronidase (Gus), which is heat‐stable, rapidly repopulated the haematopoietic compartment of irradiated recipient mice which have only low levels of a thermolabile form of this enzyme. Gus activity was found to increase progressively in the tissues of the recipients, including the liver, heart and skeletal muscle. Elevated levels were also observed in the kidney and brain. The increase in enzyme activity in the host tissues was not due to the presence of contaminating blood cells, but rather to the acquisition of new, heat‐stable enzyme from the donor bone marrow cells. High levels of Gus activity persisted for at least 72 weeks, showing the potential therapeutic value of BMT for enzyme deficiency diseases.