bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uptake and metabolism of radiolabelled GM1‐ganglioside in skin fibroblasts from controls and patients with GM1‐gangliosidosis
Authors: Midorikawa M. , Inui K. , Okada S. , Yabuuchi H. , Ogura K. , Handa S. 
Published: June 2005

SummaryThe uptake and metabolism of [3‐3H‐sphingosine]GM1‐ganglioside was measured in cultured skin fibroblasts from controls and patients with infantile, juvenile and adult GM1‐gangliosidosis. When dissolved in medium with phosphatidylserine, GM1‐ganglioside was efficiently taken up by cultured skin fibroblasts and transferred into lysosomes. A linear increase in GM1‐ganglioside endocytosis was shown with phosphatidylserine concentrations of up to 40γm/ml. A pulse‐chase study revealed that [3H]GM1‐ganglioside was metabolized to GM2‐ganglioside, GM3‐ganglioside, ceramide dihexoside, ceramide monohexoside, ceramide and sphingosine. Sphingosine was recycled to sphingomyelin. In a 20‐h pulse study, cell lines from patients with GM1‐gangliosidosis of infantile, juvenile and adult types hydrolysed 2–5%, 20–44% and 54–58% of the total endocytosed GM1‐ganglioside respectively. These values were lower than in control cells (64.17 ± 5.43% (n=10)). The hydrolysis rates of exogenous [3H]GM1‐ganglioside in cultured fibroblasts from patients with various types of GM1‐gangliosidosis closely reflected the clinical severity.
Content of phenylalanine, tyrosine and their metabolites in CSF in phenylketonuria
Authors: Antoshechkin A. G. , Chentsova T. V. , Tatur V. Yu. , Naritsin D. B. , Railian G. P. 
Published: June 2005

SummaryBy using ion‐exchange chromatography and gas chromatography coupled with mass spectrometry, the content of phenylalanine, tyrosine and their metabolites typical of phenylketonuria (PKU) was determined in the cerebrospinal fluid (CSF) of 8 untreated children with classical PKU and 9 controls. At the same time, plasma and urine were analysed. In PKU the content of phenylalanine is increased on average 23 times in plasma and CSF. The content of phenylalanine and tyrosine in CSF is about 4 times less as compared with plasma. The phenylalanine‐to‐tyrosine ratio is approximately the same for these fluids both in control and in PKU. This indicates that the transport of phenylalanine and tyrosine through the blood‐brain barrier is not disturbed in PKU.Phenylpyruvate and 4‐hydroxyphenylpyruvate are either not detected or present in very low concentrations in the CSF of children with PKU; their derivatives, phenyllactate and 4‐hydroxyphenyllactate, are present in relatively higher concentrations. This indicates increased metabolic conversion in brain tissues.
Infantile phytanic acid storage disease, a possible variant of Refsum's disease: Three cases, including ultrastructural studies of the liver
Authors: Scotto J. M. , Hadchouel M. , Odievre M. , Laudat M. ‐H. , Saudubray J. ‐M. , Dulac O. , Beucler I. , Beaune P. 
Published: June 2005

AbstractThree cases of phytanic acid storage disease with symptoms during the first months of life are reported. Hepatomegaly, facial dysmorphia, growth and/or mental retardation and osteopenia were observed in addition to retinitis pigmentosa and neurosensory deafness. The presence of phytanic acid in serum (160–320 µmol/1 (50–100 µg/ml)) was accompanied by hypocholesterolaemia. Electron microscopy showed that a storage material had accumulated in mesenchymal and parenchymal liver cells. Lamellar structures were seen in hepatocytes and other storing cells. These inclusions resembled the structures found in plant chloroplasts containing phytol.Some of the clinical and biological data obtained were consistent with Refsum's disease. However, other characteristics such as mental retardation, hepatomegaly, osteopenia, hypocholesterolaemia and hypoalphalipoproteinaemia, as well as the ultrastructural findings in the liver, suggested that our patients' illness was either a phytanic acid storage disease different from the classical form of Refsum's disease, or a more severe early symptomatic form of Refsum's disease. Early diagnosis by phytanic acid assay and electron microscopic liver examination calls for prescription of a low phytanate diet in the hope of improving the child's condition.
An occipito‐temporal syndrome in adolescents with optimally controlled hyperphenylalaninaemia
Authors: Lou H. C. , Toft P. B. , Andresen J. , Mikkelsen I. , Olsen B. , Güttler F. , Wieslander S. , Henriksen O. 
Published: June 2005

SummaryThe study included 16 adolescents with optimally controlled hyperphenylalaninaemia (McKusick 26160), of whom six did not require treatment according to conventional criteria. All except the two patients with lowest median serum phenylalanine level throughout childhood (most values at 200–300 µmol/L) had white matter abnormalities detectable with magnetic resonance imaging. The lesions were particularly prominent in the watershed regions between the posterior and middle cerebral arteries. In most patients with moderate or severe hyperphenylalaninaemia frontal white matter lesions were present as well. Normal proton magnetic resonance spectra indicated that the lesions were stable. Occipital EEG abnormalities were frequent, and deficient performance on a pattern‐recognition test was a characteristic neuropsychological finding. Serum phenylalanine levels at about 300 µmol/L or below throughout childhood and early adolescence may be required to avoid lesions. The present study demonstrates the limitations of even an optimally controlled dietary regimen in hyperphenylalaninaemia.
Investigation of enzyme defects in children with lactic acidosis
Authors: Merinero B. , Pérez‐Cerda C. , Ugarte M. 
Published: June 2005

SummaryScreening for enzyme deficiencies was carried out in cultured skin fibroblasts and leukocytes of 19 patients with lactic acidosis and neurological problems. Pyruvate carboxylase deficiency was demonstrated in three cases. Reduced pyruvate oxidation was found in seven cultures; six showed no significant stimulation of the oxidation rate by methylene blue and in three a decreased pyruvate dehydrogenase complex activity was confirmed. Methylene blue restored a near normal oxidation rate in the seventh culture which had decreased cytochromec oxidase activity.
Prenatal diagnosis of Non‐ketotic hyperglycinaemia
Authors: Toone J. R. , Applegarth D. A. , Levy H. L. 
Published: June 2005

SummaryNon‐ketotic hyperglycinaemia (NKH) is a devastating neurological disease for which there is no effective therapy. Consequently, most couples with a pregnancy known to be at risk for NKH request prenatal diagnosis. We have applied the combination of chorionic villus (CVS) assay for glycine cleavage enzyme activity and determination of amniotic fluid glycine concentration to increase the reliability of prenatal diagnosis for this disorder beyond that of each of these methods alone. All 15 of the at‐risk pregnancies monitored had CVS glycine cleavage assay and five also had amniotic fluid glycine measurements. Two cases had no detectable cleavage activity in CVS and one gave uninterpretable enzyme results. Amniotic fluid glycine concentration was increased in all three and NKH was confirmed by abortus tissue assays for cleavage activity and amino acids. The remaining 12 case had activity in CVS (two also had normal amniotic fluid glycine levels) and delivered unaffected infants. Four of these 12 cases had cleavage activities below or at the low end of the normal range, perhaps indicating carrier status. We believe that the combination of CVS glycine cleavage assay and amniotic fluid glycine measurement is currently the best approach to the prenatal diagnosis of NKH.
Measurement of acyl‐CoA dehydrogenase activity in cultured skin fibroblasts and blood platelets
Authors: Taylor R. W. , Jackson S. , Pourfarzam M. , Bartlett K. , Turnbull D. M. 
Published: June 2005

SummaryThe measurement of acyl‐CoA dehydrogenase activity is an essential part of the investigation of patients with suspected defects of fatty acid oxidation, and recently the organometallic oxidant ferricenium hexafluorophosphate has been introduced as an electron acceptor for these assays. However, we show that when medium‐chain acyl‐CoA dehydrogenase activity was measured in cultured skin fibroblasts and platelets from patients with proven defects of this enzyme, there was considerable residual enzyme activity when this electron acceptor was used. The ferricenium assay is not as specific as the anaerobic ETF‐linked assay in the biochemical diagnosis of medium‐chain acyl‐CoA dehydrogenase deficiency in fibroblasts, and therefore is of limited clinical applicability in its present form.
N‐acetylglucosamine 6‐sulphatase deficiency in a Nubian goat: A model of Sanfilippo syndrome type D (mucopolysaccharidosis IIID)
Authors: Thompson J. N. , Jones M. Z. , Dawson G. , Huffman P. S. 
Published: June 2005

SummaryA male Nubian goat (SD‐1) presented at birth with neurological manifestations consistent with a lysosomal storage disease. Histological studies of tissue obtained at autopsy suggested glycosaminoglycan storage. Total urinary glycosaminoglycan levels, as measured by the uronic acid method, were elevated but overlapped with levels in a younger control goat. However,N‐sulphate content was increased 2‐ to 5‐fold, suggestive of heparan sulphate excretion, and this elevation was confirmed by cellulose acetate electrophoresis. Further, urinary levels of freeN‐acetylglucosamine 6‐sulphate were increased 6‐fold over controls, SD‐1 cultured skin fibroblasts, labelled with [35S]sulphate, incorporated twice as much radioactivity into macromolecular material as did normal fibroblasts. Forty‐eight hours after removal of [35S]sulphate from the medium the SD‐1 fibroblasts retained 58% of the label, whereas in control fibroblasts it had declined to 20%, indicative of [35S]proteoglycan storage in SD‐1. The assay of fibroblast extracts revealed a profound deficiency ofN‐acetylglucosamine 6‐sulphatase whereas eight other activities includingβ‐mannosidase, arylsulphatase B, iduronate 2‐sulphatase,N‐acetylgalactosamine 6‐sulphatase, and heparin sulphamidase were normal. Mixing of SD‐1 sonicates with normal sonicates showed no evidence of an inhibitor, and mixing of SD‐1 sonicates with Sanfilippo D cell sonicates yielded no activity. These data ruled out multiple sulphatase deficiency and suggested the first example of the human Sanfilippo syndrome, type D (N‐acetylglucosamine 6‐sulphatase deficiency) in goats.
Serum selenium levels in individuals on PKU diets
Authors: Darling G. , Mathias P. , O'Regan M. , Naughten E. 
Published: June 2005

SummarySerum selenium levels in 73 patients with phenylketonuria were significantly lower than in controls. The phenylketonuric and hyperphenylalaninaemic individuals taking the non‐supplemented amino acid mixture generally had lower levels: 36% were below the normal range as defined by our laboratory, compared with 19% in the supplemented group. The low levels were present even in those on diet, who had a greater phenylalanine tolerance — that is, a tolerance for more than 9×50 mg phenylalanine exchanges per day, in other words a higher intake of natural protein. Individuals on long‐term synthetic diets may be at risk for selenium deficiency even on selenium supplements. In areas where the soil may be low in selenium, the deficiency may be aggravated. Long‐term low levels may impair health but the required amount of selenium supplementation remains uncertain.
Sialuria: a second case
Authors: Wilcken B. , Don N. , Greenaway R. , Hammond J. , Sosula L. 
Published: June 2005

AbstractA case of sialuria is described in a girl who presented in the neonatal period with hepatosplenomegaly, and who has moderate developmental delay at the age of 2 years. There was massive urinary excretion of free sialic acid (N‐acetylneuraminic acid). The clinical, biochemical and ultramicroscopical features were distinct from those described in Salla disease and in infantile sialic acid storage disorder.
Localization of pipecolic acid metabolism in rat liver peroxisomes: Probable explanation for hyperpipecolataemia in Zellweger syndrome
Authors: Trijbels J. M. F. , Monnens L. A. H. , Melis G. , van den Broekvan Essen M. , Bruckwilder M. 
Published: June 2005

AbstractThe metabolism of [14C]pipecolic acid was studied in peroxisomal fractions of rat liver obtained by density gradient centrifugation in Percoll. The production rate of [14CO2] was used to measure the metabolic activity of the fractions towards [14C]carboxypipecolic acid as a substrate. It was shown that this activity was located in the peroxisomal fractions by comparison with the peroxisomal marker enzyme urate oxidase (EC 1.7.3.3). The process was markedly elevated by the addition of FAD. The apparentKm forDL‐pipecolic acid was found to be 1.2 mmol L−1. Addition of ATP (1 mmol L−1) did not influence the decarboxylation rate of pipecolic acid. These results might explain the defective metabolism of pipecolic acid in patients with Zellweger syndrome who are lacking peroxisomes.
Argininosuccinic aciduria: Long‐term treatment with arginine
Authors: Parsons H. G. , Scott R. B. , Pinto A. , Carter R. J. , Snyder F. F. 
Published: June 2005

AbstractThe presentation and 2 year treatment of a patient with argininosuccinic aciduria is reported. Erythrocyte argininosuccinate lyase activity was less than 2% of normal. Long‐term management included protein restriction and arginine dietary supplementation. The child experienced three episodes of hyperammonaemia (>100 µm), the first at birth, the second at 6.5 months and the third at 16 months. Neurological development deteriorated between 14 and 24 months. Hepatomegaly and biochemical hepatitis, a feature of this condition, was accompanied by enlarged mitochondria with tubular paracrystalline inclusions not previously recognized in this disorder.
Cerebrotendinous xanthomatosis: A review of biochemical findings of the patient population in the netherlands
Authors: Koopman B. J. , Wolthers B. G. , van der Molen J. C. , van der Slik W. , Waterreus R. J. , van Spreeken A. 
Published: June 2005

SummaryThis study gives a review of the results obtained from biochemical investigations of 20 patients in The Netherlands suffering from cerebrotendinous xanthomatosis, an inborn error of metabolism in bile acid synthesis. Diagnosis can best be established by determining the excretion of urinary bile alcohols, in particular 5β‐cholestane‐3α,7α,12α,23,25‐pentol, in urine by means of capillary gas chromatography. Measurement of serum cholestanol levels or serum cholestanol/cholesterol ratios, commonly used for establishing cerebrotendinous xanthomatosis, are not reliable. The effectiveness of the different therapies, i.e. administration of bile acids, can be evaluated by monitoring the urinary excretion of bile alcohols. From such investigations it was concluded that cholic acid especially, but also chenodeoxycholic acid are the therapies of choice for the treatment of cerebrotendinous xanthomatosis. All patients, until now diagnosed in The Netherlands were not discovered before the third or fourth decade of life because the characteristic signs only then become manifest clearly. Unfortunately, because sterol storage is almost irreversible, therapy only results in minor improvements of the patient's condition. Therefore early detection of the presence of cerebrotendinous xanthomatosis is desirable so that treatment can start before extensive storage of sterols is a fact. We developed some laboratory assays with the purpose of early detection. One consists of the detection of cerebrotendinous xanthomatosis carriers by subjecting them to oral cholestyramine administration and monitoring the urinary excretion of the bile alcohol 5β‐cholestane‐3α,7α,12α,23,25‐pentol before and after treatment. Secondly, a relatively simple screening test for cerebrotendinous xanthomatosis was developed based on an enzymatic assay of 7α‐hydroxylated steroids in urine. After suitable modification this assay in principle allows the screening of large populations for the existence of cerebrotendinous xanthomatosis and thus to detect the disease at an earlier stage of life.
Effect of the X‐linkedHyp mutation onN‐ethylmaleimide labelling of proteins in renal brush border membrane
Authors: Vizel E. J. , Tenenhouse H. S. , Scriver C. R. 
Published: June 2005

SummaryThe X‐linked dominant mutation, hypophosphataemia (gene symbol,Hyp) is expressed in the laboratory mouse as deficient phosphate transport at the renal brush border membrane (BBM) of proximal nephron. In an attempt to identify proteins which mediate phosphate transport, we treated renal BBM vesicles prepared from mutant male (Hyp/Y) and normal male (+/Y) littermates, with radiolabelledN‐ethylmaleimide (NEM), in the presence or absence of arsenate which is a competitive inhibitor of phosphate transport. Polyacrylamide gel electrophoresis revealed labelling of membrane proteins in the 40–45 kDa range; addition of arsenate during NEM treatment inhibited labelling. These findings indicate a 40–45 kDa protein as a component of the renal BBM phosphate transport system(s). We found no difference between protein labelling of the renal BBM fromHyp/Y and +/Y mice.
Review: Genetics of steroid sulphatase deficiency and X‐linked ichthyosis
Authors: Crawfurd M. A. 
Published: June 2005

AbstractSteroid sulphatase deficiency which started out as a curious placental microsomal enzyme deficiency associated with low maternal urinary oestrogen excretion and difficulties in delivery, first described only twelve years ago, has now become a generalized enzyme deficiency associated also with a common skin disease. It turns out not only to be inherited in an X‐linked recessive manner, but to be part of a gene cluster which includes the Xg blood group gene and which has been precisely assigned to the distal tip of the short arm of the X‐chromosome. This cluster is unique for genes on the X‐chromosome in escaping X‐inactivation.It remains to be unequivocally demonstrated whether steroid sulphatase is identical to arylsulphatase C or whether these are two enzymes sharing a common polypeptide chain determined by a single gene. However, Rose (1982) presents evidence that one steroid sulphatase is probably identical with arylsulphatase C. It also remains to be conclusively demonstrated whether the gene for the enzyme deficiency is also that for ichthyosis or whether they are two very closely linked genes. If the former is true the role of steroid sulphatase in the abnormal keratinization of ichthyosis is still to be elucidated. Above all the special nature of the DNA in this unique region awaits description.
Pterins analysis in amniotic fluid for the prenatal diagnosis of GTP cyclohydrolase deficiency
Authors: Dhondt J. ‐L. , Tilmont P. , Ringel J. , Farriaux J. ‐P. 
Published: June 2005

SummaryHyperphenylalaninaemia due to tetrahydrobiopterin deficiency is a group of rare and severe diseases. Prenatal diagnosis of dihydropteridine reductase and pyruvoyltetrahydropterin synthetase deficiencies can be achieved by enzyme assay in cultured fluid cells and/or fetal blood. In contrast, prenatal diagnosis of GTP cyclohydrolase deficiency can only rely on the measurement of pterin metabolites in the amniotic fluid.A pregnancy at risk for GTP cyclohydrolase deficiency was investigated. HPLC analysis of amniotic fluid pterins revealed neopterin and biopterin concentrations below the lowest limit of normal age‐matched gestations. The mother refused abortion. The early follow‐up of the child confirmed the diagnosis of GTP cyclohydrolase deficiency (hyperphenylalaninaemia, abnormal profile of urinary pterins and neurological deterioration).
Relationship between plasma and red cell biopterins in acute and chronic hyperphenylalaninaemia
Authors: Leeming R. J. , Hall S. K. , Surplice I. M. , Green A. 
Published: June 2005

SummaryBiopterin concentrations in red blood cells were higher in patients with chronic hyperphenylalaninaemia than following a single oral dose of phenylalanine, although the plasma concentrations were similar. These findings suggest that tetrahydrobiopterin is synthesized in immature red blood cells in response to hyperphenylalaninaemia. The less marked increase in plasma biopterin suggests slow release from a tissue reservoir. The maintenance of a differential between erythrocyte and plasma biopterin concentrations suggests that some mechanism retains biopterin intracellularly.
Increased plasma pyridoxal‐5′‐phosphate levels before and after pyridoxine loading in carriers of perinatal/infantile hypophosphatasia
Authors: Chodirker B. N. , Coburn S. P. , Seargeant L. E. , Whyte M. P. , Greenberg C. R. 
Published: June 2005

SummaryWe measured plasma levels of pyridoxal‐5′‐phosphate (PLP), a cofactor form of vitamin B6 and apparent natural substrate for alkaline phosphatase (ALP), in carriers and in non‐carriers of the severe perinatal and infantile forms of hypophosphatasia, both before and after an oral load of pyridoxine (i.e. 1/3 mg/kg body weight). The assignment of carrier status was determined by serum ALP activity, level of serum inorganic phosphate, and if necessary urinary phosphoethanolamine excretion. Plasma PLP levels were significantly increased in the carriers both before and especially after B6 loading.
Erythrocytic uridine diphosphate galactose in galactosaemia
Authors: Kirkman H. N. 
Published: June 2005

SummaryAn earlier claim of a deficiency of uridine diphosphate galactose in erythrocytes of galactosaemia patients was not confirmed. Enzymic techniques similar to those of the earlier investigators were used to determine not only the concentration of uridine diphosphate galactose but also the ratio of this concentration to the sum of the uridine sugar diphosphates (uridine diphosphate galactose and uridine diphosphate glucose). The values in erythrocytes of galactosaemic subjects were similar to those of non‐galactosaemic children on a galactose‐restricted diet and to those of normal adults. These results cast doubt on the claim of a major deficiency of uridine diphosphate galactose in galactosaemia and on the need for treating galactosaemic children with uridine.
Animal models for lysosomal storage diseases: A new case of feline mucopolysaccharidosis VI
Authors: Di Natale P. , Annella T. , Daniele A. , Spagnuolo G. , Cerundolo R. , de Caprariis D. , Gravino A. E. 
Published: June 2005

SummaryTwo long‐haired Siamese cats are reported with clinical manifestations of human mucopolysaccharidosis VI (Maroteaux‐Lamy disease): facial dysmorphia, dysostosis multiplex, paralysis. Urine of the two affected animals contained a high concentration of glycosaminoglycans, as detected by the dimethylmethylene blue test. Qualitative analysis, performed by thin‐layer chromatography of the cetylpyridinium chloride‐precipitable material, showed dermatan sulphate. Excessive incorporation of [35S]sulphate in the intracellular mucopolysaccharide of cultured fibroblasts and deficiency of arylsulphatase B in such cells indicate that these cats are affected by Maroteaux‐Lamy disease. They should thus be considered the first European case of feline mucopolysaccharidosis VI.