bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in cholesterol metabolism in cultured fibroblasts from patients with Niemann‐Pick disease type C
Authors: Mazière C. , Mazière J. C. , Mora L. , Lageron A. , Polonovski C. , Polonovski J. 
Published: June 2005

SummaryCholesterol synthesis, esterification and efflux were investigated in cultured fibroblasts from patients with Niemann‐Pick disease type C. Sterol synthesis from sodium acetate was markedly increased in the two Niemann‐Pick disease type C strains as compared to controls, either in the presence or absence of exogenous cholesterol supply by low‐density lipoproteins. By contrast, cholesterol esterification was about 2–3‐fold reduced when measured by oleic acid incorporation into cholesteryl esters and 10–15‐fold reduced when measured with labelled free cholesterol as precursor, although acylcoenzyme‐A: cholesterol acyltransferase activity was normal when studiedin vitro on cell homogenates. Chase experiments with14C‐cholesterol demonstrated that the rate of cholesterol efflux was decreased by about 3–4‐fold in fibroblasts from patients with Niemann‐Pick disease type C. These results provide further evidence for alterations of sterol metabolism in Niemann‐Pick disease type C and support the hypothesis of a trapping of exogenous cholesterol, which cannot enter the regulatory intracellular pools.
Hyperammonaemia and lactic acidosis in a patient with pyruvate dehydrogenase deficiency
Authors: Brown G. K. , Scholem R. D. , Hunt S. M. , Harrison J. R. , Pollard A. C. 
Published: June 2005

SummaryA patient who presented in the newborn period with severe lactic acidosis and hyperammonaemia has been shown to have a specific defect in the pyruvate dehydrogenase complex. The secondary inhibition of ureagenesis in this patient appears to be due to a functional deficiency of carbamyl phosphate synthetase.
Urinary organic acids in succinic semialdehyde dehydrogenase deficiency: Evidence of α‐oxidation of 4‐hydroxybutyric acid, interaction of succinic semialdehyde with pyruvate dehydrogenase and possible secondary inhibition of mitochondrial β‐oxidation
Authors: Brown G. K. , Cromby C. H. , Manning N. J. , Pollitt R. J. 
Published: June 2005

SummaryIn addition to the previously reported abnormalities, urine extracts from three cases of succinic semialdehyde dehydrogenase deficiency have shown consistently increased amounts of 2,4‐dihydroxybutric acid, and its lactone, and 3‐hydroxypropionic acid, metabolites related to the α‐oxidation of 4‐hydroxybutyric acid.Threo‐ anderythro‐4,5‐dihydroxyhexanoic acids have also been identified for the first time and probably arise from the reaction of succinic semialdehyde with an intermediate in the pyruvate dehydrogenase pathway. Adipic acid excretion is also consistently raised, suggesting secondary interference with mitochondrial β‐oxidation. The presence of these metabolites could be a source of diagnostic confusion.
Amniotic fluid propionylcarnitine in methylmalonic aciduria
Authors: Penn D. , Schmidt‐Sommerfeld E. , Jakobs C. , Bieber L. L. 
Published: June 2005

SummaryAmniotic fluid samples from pregnancies complicated by foetal methylmalonic aciduria and from metabolically normal pregnancies were obtained at 16–18 weeks of gestation and analysed for total, free and acylcarnitine and individual carnitine esters. The amniotic fluid concentrations of total acylcarnitine and propionylcarnitine were higher in pregnancies with methylmalonic aciduria than in normal pregnancies. The predominant carnitine ester was propionylcarnitine in the methylmalonic aciduria group and acetylcarnitine in the normal group. These findings suggest that in methylmalonic aciduria, abnormalities of carnitine metabolism already occur early in gestation. The amount of propionylcarnitine in amniotic fluid may be useful as an additional indicator of foetal methylmalonic aciduria
Urinary D‐4‐hydroxyphenyllactate, D‐phenyllactate and D‐2‐hydroxyisocaproate, abnormalities of bacterial origin
Authors: Spaapen L. J. M. , Ketting D. , Wadman S. K. , Bruinvis L. , Duran M. 
Published: June 2005

SummaryAnalysis of urinary organic acids in patients admitted for screening for inborn errors of metabolism incidentally revealed the presence of abnormal amounts of 4‐hydroxyphenyllactate (4‐HPLA) and phenyllactate (PLA). These compounds are found in tyrosinaemia and phenylketonuria but in our patients such disorders could not be established. By means of configuration analysis it was shown that these 2‐hydroxyacids consisted partly of theD‐enantiomers, pointing to a bacterial origin. Endogenously formed urinary 2‐hydroxyacids in tyrosinaemia or phenylketonuria consisted of only theL‐enantiomers. Furthermore, the urine of a patient with an established short bowel syndrome contained a wide variety of bacterial amino acid metabolites, including 2‐hydroxyisocaproic acid (2‐HICA). In this case 2‐HICA occurred predominantly in theD‐form whereas in the urine of a patient with maple syrup urine disease this compound appeared to have theL‐configuration.
Increased urinary excretion of putrescine in hyperargininaemia
Authors: Kato T. , Sano M. , Mizutani N. , Hayakawa C. 
Published: June 2005

SummaryA 4‐year‐old boy with hyperargininaemia had an increased urinary excretion of putrescine which was exaggerated with oral ornithine supplementation. It seems unlikely that putrescine was overproduced within the gut, because a loading with a single oral dose of ornithine showed that the intestinal ornithine absorption in the patient was normal. An acceleration of extramitochondrial ornithine metabolism due to impaired mitochondrial ornithine uptake may have caused the hyperexcretion of putrescine.
Cerebrotendinous xanthomatosis: a defect in cellular sterol biosynthetic control
Authors: Barron J. L. , Maxwell J. U. , Rutherfoord G. S. 
Published: June 2005

AbstractA mentally retarded woman with tendon xanthomata and normal serum cholesterol concentration was found to have raised cholestanol concentrations in the serum and in a xanthoma. This confirmed the diagnosis of cerebrotendinous xanthomatosis (CBX). No specific lipoprotein fraction was found to transport cholestanol. For the first time cultured fibroblasts from a patient with CBX were found to accumulate cholestanol.
Treatment of hyperargininaemia due to arginase deficiency with a chemically defined diet
Authors: Cederbaum S. D. , Moedjono S. J. , Shaw K. N. F. , Carter M. , Naylor E. , Walzer M. 
Published: June 2005

AbstractA brother and sister aged 11 and 17 years have been reported previously to have hyperargininaemia and arginase deficiency: they were treated with a semi‐synthetic diet consisting of fat, carbohydrate, minerals, vitamins and essential amino acids in amounts equivalent to 0.55–0.65 g protein kg−1 day−1 for 2 years. Plasma arginine levels fell from 0.50–0.90 µmol/l to 0.13–0.30 µmol/l (normal range 0.02–0.15). Increased concentrations of arginine in the cerebrospinal fluid (CSF) fell from 0.069–0.098 µmol/l to 0.040–0.056 µmol/l (normal mean ± SD=0.020±0.006). Dibasic aminoaciduria returned to normal within 1 week. Substitution of the keto‐acid analogues of five essential amino acids in the formula lowered arginine concentrations further, but proved to be unpalatable. Urinary concentrations of orotic acid, uridine and uracil fell toward normal but remained increased, even when the plasma ammonia concentration was measured as normal. Both patients showed a stable clinical improvement.
Zinc status and growth of children undergoing treatment for phenylketonuria
Authors: Acosta P. B. , Fernhoff P. M. , Warshaw H. S. , Elsas L. J. , Hambidge K. M. , Ernest A. , McCabe E. R. B. 
Published: June 2005

AbstractChildren with phenylketonuria (PKU) are treated with semi‐synthetic diets restricted in phenylalanine. Low‐phenylalanine or phenylalanine‐free formulae provide the majority of protein and energy in the diet while phenylalanine requirements are met by low‐protein natural foods. Because of the restriction of natural protein sources in this diet, the study assessed the zinc nutrition of 22 treated children with PKU (aged from 1 month to 8 1/2 years) and correlated linear growth with zinc status.The mean (±SE) plasma zinc concentration of the PKU population was 66.6±3.3 µg/dl. The mean (±SE) hair zinc concentration was 70.2±11.5 µg/g. The mean plasma and hair zinc concentrations of the PKU population were significantly different (p<0.05) when compared with mean (±SE) normal values of 84.2±2.9 µg/dl and 130.7±8.3 µg/g, respectively. The mean (±SD) dietary zinc intake of 10 PKU patients was 8.56±2.68 mg/day. No significant differences (p<0.123) were found when the mean zinc intake was compared with National Academy of Sciences Recommended Dietary Allowance for age of 10 mg/day. No significant correlations were found when plasma and hair zinc concentrations were plotted with height percentiles. Further studies are required to assess the effects of zinc supplementation and the bioavailability of zinc from low‐phenylalanine diets.
Normal hydroxylation of proline in collagen synthesized by skin fibroblasts from a patient with prolidase deficiency
Authors: Royce P. M. , Danks D. M. 
Published: June 2005

AbstractThe extent of hydroxylation of proline in collagen synthesized and secreted into the culture medium by skin fibroblasts derived from a patient with prolidase deficiency has been examined and found to be normal. It would seem likely that to a considerable extent the urinary proline‐containing dipeptides apparent in this condition are derived from sources other than collagen.
Cell genetic studies on propionyl‐CoA carboxylase deficient cell lines
Authors: van Leeuwen G. H. , de Vrieze G. , Gimpel J. A. , Huisjes H. J. , Hommes F. A. 
Published: June 2005

AbstractThirteen propionyl‐CoA carboxylase (PCC)‐deficient fibroblast lines were analysed for complementation by examining the incorporation of [14C]propionate into trichloroacetic‐acid insoluble cellular macromolecules of polyethylene‐glycol‐dimethyl‐sulphoxide induced heterokaryons formed by fusion of mutant cell lines. Corrections for variations in the rate of protein synthesis of the heterokaryons and individual cell lines was made by measuring the incorporation of [3H]lysine, added simultaneously with the labelled propionate.Two distinct complementation groups were found in this sample of PCC‐deficient cell lines. Evidence for intragenic complementation was not obtained.
Dietary treatment and biochemical studies on a neonatal case of propionyl‐CoA carboxylase deficiency
Authors: Del Valle J. A. , Merinero B. , Jiménez A. , García M. J. , Ugarte M. , Omeñaca F. , Neustadt G. , Quero J. 
Published: June 2005

AbstractThe case of a patient with neonatal propionic acidaemia is reported. Despite an initially favourable response to the administration of an artificial formula, the patient finally died when 9.5 months old. Protein tolerance never exceeded 1.3 g kg−1 day−1. During the remission periods, when ingesting the formula, 3‐hydroxypropionic acid was excreted alone or together with tiglylglycine and/or methylcitrate. In a period of ketoacidosis, in addition to these three metabolites and those of ketoacidosis, elevations of 2‐methyl‐3‐oxovaleric acid, propionylglycine and 2‐methyl‐3‐hydroxybutyric acid were found. A severe deficiency of propionyl‐CoA carboxylase in cultured fibroblasts was detected; biotin, when added to the fibroblasts culture media, did not stimulate this enzyme activity. The effectiveness of the administered formula is discussed.
Carrier detection in glutaric aciduria type I using interleukin‐2‐dependent cultured lymphocytes
Authors: Seargeant L. E. , Chudley A. E. , Dilling L. A. , Mallory C. J. , Haworth J. C. 
Published: June 2005

SummaryCultured interleukin 2 (IL‐2)‐dependent leukocytes from 13 patients with glutaric aciduria type I, 12 obligate carriers, 105 family members and 31 normal controls were assayed for glutaryl‐CoA dehydrogenase activity. Of the 13 affected patients, 10 (all Ojibway Indian) had residual enzyme activity (2–13% of control) and 3 patients (all non‐Indian) had undetectable enzyme activity. There was partial overlap between the distribution of enzyme activity in obligate heterozygotes and in normal controls (mean values±SD: 6.29±0.94 and 10.75±2.58 nmol/h per mg protein respectively). Using an arbitrary cutoff level of <7 nmol/h per mg protein as presumptive evidence of carrier status, the observed frequency of carriers did not differ significantly from that expected from theira priori risk of carrier status. Thirteen per cent of the family members had inconclusive status (activity between 7 and 8.5 nmol/h per mg protein). The method appears suitable for carrier detection, although definitive carrier assignment awaits identification of the mutation(s) responsible for glutaric aciduria type I.
Characterization of phosphofructokinase‐deficient canine erythrocytes
Authors: Harvey J. W. , Pate M. G. , Mhaskar Y. , Dunaway G. A. 
Published: June 2005

SummaryDogs homozygously affected with muscle‐type phosphofructokinase (PFK) deficiency had about 20% of normal erythrocyte PFK activity and exhibited a compensated haemolytic anaemia. Erythrocyte glucose‐6‐phosphate and fructose‐6‐phosphate concentrations were increased and dihydroxyacetone phosphate and 2,3‐bisphosphoglycerate values were below normal in affected dogs. Other intermediates distal to the PFK step were not significantly below normal and fructose‐1,6‐bisphosphate was even above normal. Erythrocyte ATP was higher than normal in affected dogs owing to the reticulocytes present. Abnormal adenylate metabolism was demonstrated by low ATP/AMP and ADP/AMP ratios and the inability to maintain ATP content when affected erythrocytes were incubated with cyanide. Glucose‐1,6‐bisphosphate content was normal, and fructose‐2,6‐bisphosphate content in affected canine erythrocytes was higher than normal. Studies of erythrocyte PFK isozymes revealed altered enzyme kinetic properties in affected dogs which appeared to be due to the loss of the M‐type subunit.
Plasma lipoproteins and monocyte‐macrophages in a peroxisome‐deficient system: Study of a patient with infantile refsum disease
Authors: Mandel H. , Berant M. , Meiron D. , Aizin A. , Oiknine J. , Brook J. G. , Aviram M. 
Published: June 2005

SummaryHypocholesterolaemia in infantile Refsum disease (IRD) may link peroxisomes and lipoprotein metabolism. In our patient, plasma cholesterol levels were reduced to 26% and 29% of control in LDL and HDL fractions, respectively. Plasma apolipoproteins B‐100 and A‐I levels were 52% and 66% of controls, respectively. In the kindred, plasma cholesterol concentration was 61–73% of controls. The HDL‐cholesterol/apo A‐I ratios were: patient 0.12; kindred 0.17; controls 0.28.Analysis of the IRD patient's lipoprotein revealed compositional abnormalities in all fractions. The patient's LDL demonstrated a substantial reduction in its lipid‐to‐protein ratio. Alterations in plasma lipoproteins affect their interaction with macrophages. Upon incubation of the patient's LDL with J‐774 macrophages, its cellular uptake, measured as cholesterol esterification rate, was only 66% of a control rate. The abnormal LDL of the IRD patient showed also only 25% of control susceptibility toin vitrooxidation. Studies of cellular cholesterol metabolism in the patient's monocyte‐derived macrophages (MDM) showed 57% increased cholesterol esterification rate in comparison to normal MDM. The possible link between lipoprotein abnormalities and monocyte‐macrophage cholesterol metabolism is discussed.
Complementation studies with clinical and biochemical characterizations of a new variant of multiple sulphatase deficiency
Authors: Tanaka A. , Hirabayashi M. , Ishii M. , Yamaoka S. , Kawamura M. , Nishida M. , Isshiki G. 
Published: June 2005

AbstractA patient with a new variant of multiple sulphatase deficiency (MSDv) is reported. Unlike the usual type, onset was late and progress was slow. The phenotypic changes were those usually seen in multiple sulphatase deficiency but much milder. Cytoplasmic accumulations were found in skin fibroblasts, and urinary mucopolysaccharides and sulphatides were high. Arylsulphatases A, B and C (ASA, B and C), heparan N‐sulphatase sulphoiduronate sulphatase, andN‐acetylgalactosamine 6‐sulphatase all had low activity in lymphocytes and cultured skin fibroblasts. Complementation for ASA activity was found in hybrids between MSDv and metachromatic leukodystrophy (MLD) as well as between multiple sulphatase deficiency (MSD) and MLD. Complementation for ASC activity was also seen in hybrids between MSDv and X‐linked ichthyosis (XLI), and between MSD and XLI. However, neither ASA nor ASC activity increased in hybrid cells of MSDv and MSD. These results suggested that the mutations of MSDv and of MSD were allelic, although of different phenotypes.
Elevation of serum β‐hexosaminidase and α‐d‐mannosidase in type 2 gaucher disease: a clinical and biochemical study
Authors: Chitayat D. , Nakagawa S. , Marion R. W. , Sachs G. S. , Shinnar S. , Llena J. F. , Nitowsky H. M. 
Published: June 2005

AbstractWe report a case of a black infant who died at 9 months of age with clinical and pathological findings consistent with the acute neuronopathic form of Gaucher disease (Type 2). Analysis of peripheral blood platelets obtained from this child demonstrated very low levels of β‐glucosidase activity. β‐hexosaminidase (HEX) activity in the serum, however, was 30 times greater than the level in control sera and 15 times greater than the level observed in individuals affected with the chronic form of Gaucher disease (Type 1). Similarly, α‐d‐mannosidase (MANN) activity in the proband's serum was significantly elevated when compared with controls, and chronic Gaucher disease patients. We postulate that the cause of the elevation of these lysosomal enzymes is similar to the cause of elevation in Type 1 individuals but that patients with Type 2 Gaucher disease have a more serious cellular defect.
3‐Hydroxy‐3‐methylglutaric aciduria: Response to carnitine therapy and fat and leucine restriction
Authors: Dasouki M. , Buchanan D. , Mercer N. , Gibson K. M. , Thoene J. 
Published: June 2005

AbstractA female infant, born to first cousin parents, lapsed into coma with severe metabolic acidosis on day three of life. The gas chromatographic/mass spectrometric urinary organic acid profile showed marked elevation of the leucine metabolites 3‐hydroxy‐3‐methylglutaric, 3‐methylglutaconic, 3‐methylglutaric and 3‐hydroxy‐isovaleric acids. Less than 5% of the normal activity of the enzyme 3‐hydroxy‐3‐methylglutaryl CoA lyase was detected in cultured skin fibroblasts. The patient's total and free carnitine was initially low but rose to normal levels after placing her ondl‐carnitine (100 mg kg−1 d−1). On a diet providing 87 mg kg−1 d−1 of leucine and only 25% of total calories as fat and 2 g kg−1 d−1 protein, the concentration of the urinary organic acids fell markedly. She is now 15 months old with normal growth and development. This regimen appears effective in the early treatment of 3‐hydroxy‐3‐methylglutaric aciduria.
Haemodialysis for metabolic decompensation in propionic acidaemia
Authors: Roth B. , Younossi‐Hartenstein A. , Skopnik H. , Leonard J. V. , Lehnert W. 
Published: June 2005

AbstractDuring an acute respiratory infection, a 4‐year‐old girl with propionic acidaemia deteriorated rapidly, becoming comatose with a marked acidosis. She did not respond to standard treatment but during haemodialysis her clinical state quickly improved.
Use of intact erythrocytes in the diagnosis of inherited purine and pyrimidine disorders
Authors: Fairbanks L. D. , Simmonds H. A. , Webster D. R. 
Published: June 2005

AbstractThis paper reports the detection of five inherited disorders of purine and one of pyrimidine metabolism using intact red blood cells (RBCs) and compares the findings with those from RBC lysate activity. Two different phosphate levels (1 and 18 mmol L−1 Pi) were used to evaluate endogenous PP‐ribose‐P levels and their generation by PP‐ribose‐P synthetase. The importance of this dual approach is demonstrated by the following evidence:

Six out of eight patients with no detectable hypoxanthine‐guanine phosphoribosyltransferase (HGPRT) RBC lysate activity had up to 25% of normal activity in their intact RBCs. Two Lesch‐Nyhan patients showed no detectable activity in intact or lysed RBCs.

RBC lysates from two heterozygotes for adenosine deaminase (ADA) deficiency also showed no detectable activity, but up to 60% of normal activity using intact RBCs.

The existence of an aberrant enzyme in a kindred with a superactive PP‐ribose‐P synthetase was evident from the fact that intact RBCs failed to respond normally to phosphate activation, despite normal HGPRT and adenine phosphoribosyltransferase (APRT) RBC lysate activity.

Raised endogenous PP‐ribose‐P levels in intact RBCs were demonstrable only in purine nucleoside phosphorylase (PNP) and HGPRT deficiency; levels were normal in APRT deficiency and hereditary oroticaciduria (OPRT/ODC) deficiency.
The results indicate that diagnosis from RBC lysate activity alone may be misleading. Intact RBC studies clearly provide a better indication of the functional capacity of the enzymein vivo. They also show a closer correlation with the clinical phenotype and allow further insight into the associated biochemical abnormalities in some cases.
Human β‐mannosidase deficiency: Biochemical findings in plasma, fibroblasts, white cells and urine
Authors: Cooper A. , Hatton C. , Thornley M. , Sardharwalla I. B. 
Published: June 2005

SummaryMarked deficiencies of β‐mannosidase activity were demonstrated in plasma, leukocytes, fibroblasts and urine of a patient with β‐mannosidosis, similar deficiencies were observed in the proband's sibling. All other lysosomal enzymes measured, including sulphamidase, exhibited normal activity. Both parents showed reduced plasma and leukocyte β‐mannosidase activity. Urinary glycosaminoglycan excretion was normal but TLC of urinary oligosaccharides revealed an abnormal band with the mobility of a disaccharide. This finding was confirmed by Bio‐Gel P2 column chromatography. Further purification of this compound revealed two disaccharides, both of which yielded mannose and glucosamine following acid hydrolysis and mannose andN‐acetylglucosamine following enzymic digestion. These two compounds are thought to be structural isomers of the disaccharide Manβ‐GlcNAc.
3‐hydroxy‐3‐methylglutaryl‐coenzyme a lyase deficiency: Report of five new patients
Authors: Gibson K. M. , Breuer J. , Kaiser K. , Nyhan W. L. , McCoy E. E. , Ferreira P. , Greene C. L. , Blitzer M. G. , Shapira E. , Reverte F. , Conde C. , Bagnell P. , Cole D. E. C. 
Published: June 2005

SummaryFive new patients are reported and the pathogenesis of the hypoglycaemia without ketogenesis is discussed. This report extends a recent review.J. Inher. Metab. Dis. 9, 225–233.