bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excessive excretion of β‐alanine and of 3‐hydroxypropionic,R‐ andS‐3‐aminoisobutyric,R‐ andS‐3‐hydroxyisobutyric andS‐2‐(hydroxymethyl)butyric acids probably due to a defect in the metabolism of the corresponding malonic semialdehydes
Authors: Pollitt R. J. , Green A. , Smith R. 
Published: June 2005

AbstractA new metabolic disorder characterised by the excessive excretion of β‐alanine, 3‐hydroxypropionic acid,R‐andS‐3‐amino‐ and 3‐hydroxyisobutyric acids andS‐2‐(hydroxymethyl)butyric acid is probably due to deficient activities of malonic, methylmalonic and ethylmalonic semialdehyde dehydrogenases. These dehydrogenation reactions could be mediated by one enzyme, or by enzymes with a common subunit, and bothR‐ andS‐methylmalonic semialdehydes seem to be equally affected. The patient is now aged 4 years and has developed normally. He has a persistent gross hypermethioninaemia which is probably unrelated to the other biochemical abnormalities.
Dolichol metabolism in cultured skin fibroblasts from patients with “neuronal” ceroid lipofuscinosis (Batten's disease)
Authors: Paton B. C. , Poulos A. 
Published: June 2005

AbstractDolichol metabolism was investigated in skin fibroblast cultures from normal individuals and patients with Batten's disease. Incorporation of [3H]mevalonolactone and [14C]acetate into the dolichol fraction of total lipid extracts was similar in cells from normal individuals and patients with Batten's disease. [14C]Acetate incorporation into dolichol in non‐saponifiable lipid extracts was compared with incorporation into dolichol in total lipid extracts, and no difference in the proportion of dolichol esterified to fatty acids was found in Batten's cells as compared to normal cells. The rate of loss of radioactivity from the dolichol pool after prelabelling with [14C]acetate was also similar in cells from Batten's and normal individuals. Thus, in the fibroblast system used, no evidence was found to support the hypothesis that Batten's disease is due to a defect in dolichol metabolism.
Immunochemical study of ornithine transcarbamylase deficiency
Authors: Kodama H. , Nagayama H. , Shimoizumi H. , Okabe I. , Kamoshita S. 
Published: June 2005

AbstractDeficiency of ornithine transcarbamylase (OTC, EC 2.1.3.3) (McKusick 31125), a mitochondrial enzyme of the urea cycle, appears to be one of the most frequent causes of inherited ammonia intoxication, and evidence indicates that the enzyme is X‐linked. Recently, different kinds of mutation have been reported (Cathelineauet al., 1972; Briandet al., 1982). We carried out detailed studies on the molecular properties of the enzyme from two heterozygous females, using an antibody to bovine OTC which cross‐reacted with the human enzyme.
Homocysteine, factor VII and antithrombin III in subjects with different gene dosage for cystathionine β‐synthase
Authors: Brattström L. , Israelsson B. , Tengborn L. , Hultberg B. 
Published: June 2005

SummaryCystathionine β‐synthase deficiency results in severe homocysteinaemia, precocious arteriosclerosis and frequent thromboembolism. In addition, antithrombin III activity and factor VII are low. Arteriosclerosis seems to be increased in heterozygotes as well (cystathionine β‐synthase gene dosage 50%) but rare in Down syndrome (cystathionine β‐synthase gene dosage 150%). In the present study total plasma homocysteine was high in three homozygotes, slightly increased in 20 obligate heterozygotes but not reduced in nine subjects with Down syndrome when compared to controls. After methionine loading, increases of homocysteine were pathologically high in 14 of 20 heterozygotes but was not, as expected, low in subjects with Down syndrome. Antithrombin III activity and factor VII antigen tended to be low in homozygotes but were normal in heterozygotes. In Down syndrome antithrombin III activity was reduced and factor VII antigen normal. There were no correlations between levels of homocysteine, antithrombin III activity and factor VII antigen. Thus, subjects with Down syndrome seem not to exhibit the expected gene dosage effect on homocysteine metabolism which could explain their reduced proneness to develop arteriosclerosis, nor do antithrombin III activity or factor VII antigen seem to be related to homocysteine metabolism.
Molecular analysis of a human liver mitochondrial ornithine transcarbamylase deficiency
Authors: Berrez J.‐M. , Bardot O. , Thiard M.‐C. , Alvarez F. , Latruffe N. 
Published: June 2005

SummaryThe liver of a young girl which had been successfully transplanted was investigated at the ornithine transcarbamylase (OTC, EC 2.1.3.3) gene expression level. Northern blot hybridization using a human OTC cDNA probe showed a greater than 80% decrease in specific OTC mRNA although having the same molecular size as a normal control. OTC polypeptide was simultaneously synthesized with a normal molecular size but at a low level (20%) as shown by immunoblotting. The OTC enzyme from the deficient liver exhibited very little catalytic activity (7.2% as compared to the normal subject). These results may support several explanations of this disease such as mutation of the OTC gene promoter leading to a low transcriptional activity or mutation of the encoding sequence which results in a modified translation product but with a normal size. mRNA instability may also occur.
Neonatal cardiomyopathy and lactic acidosis responsive to thiamine
Authors: Bakker H. D. , Scholte H. R. , Luyt‐Houwen I. E. M. , van Gennip A. H. , Abeling N. G. G. M. , Lam J. 
Published: June 2005

SummaryA congestive cardiomyopathy was diagnosed in a girl at the age of 4 weeks. In the weeks following she developed general muscle hypotonia and plasma lactate increased to 8.5 mmol/L. Biochemical investigations of a muscle biopsy at the age of 3 months showed a deficiency in the oxidation of all substrates tested: pyruvate plus malate, 2‐ketoglutarate and palmitate plus malate. After freezing and thawing of the homogenate and the addition of essential cofactors, the oxidation of the ketoacids normalized. The oxidation defect in the untreated homogenate can be explained by a deficiency in one of the cofactors (such as thiamine pyrophosphate, NAD+or CoASH), or by a defect in the oxidative phosphorylation. Treatment with thiamine and carnitine resulted in a decrease in blood lactate to normal levels and a dramatic clinical improvement. Suspension of thiamine caused deterioration of her clinical condition and lactic acidaemia. The thiamine therapy was then continued. The girl is now 6 years old and in perfect health.
Hyperglycaemia associated with lactic acidaemia in a renal allograft recipient with type I glycogen storage disease
Authors: Chen Y.‐T. , Scheinman J. I. 
Published: June 2005

SummaryRenal disease is a frequent and serious complication of type I glycogen storage disease. A type I glycogen storage disease patient with focal segmental glomerulosclerosis and progressive renal insufficiency underwent a renal allograft transplantation. Despite the same cornstarch therapy, the post‐transplantation course was complicated by worsening of the metabolic control manifested by exacerbated lactic acidaemia and hyperlipidaemia. This lactic acidaemia was remarkable for its association with hyperglycaemia. Hyperglycaemia accompanied by lactic acidaemia is strikingly unusual in type I glycogen storage disease, since this is a disease characterized by hypoglycaemia and an inverse relationship between blood glucose concentration and lactate levels. Both fasting insulin and C‐peptide levels in the patient were greater than similar age‐matched type I glycogen storage disease controls, indicating hyperinsulinaemia. The most likely mechanism responsible for the combined hyperglycaemia and lactic acidaemia was insulin resistance due to glucocorticoid treatment, instituted for immunosuppression. The hyperglycaemia associated with the lactic acidaemia was transient and resolved with steroid tapering. The exacerbated hyperlipidaemia, however, persisted after renal transplantation. Type I glycogen storage disease patients may be prone to glucocorticoid‐induced insulin resistance, since the cellular metabolism in these patients may already be compromised with ineffective insulin action and/or reduced insulin output.
Effects of deoxyadenosine on ribonucleotide reductase in adenosine deaminase‐deficient lymphocytes
Authors: Takeda E. , Kuroda Y. , Naito E. , Yokota I. , Saijo T. , Hirose M. , Miyao M. 
Published: June 2005

SummaryTo explore the relationship between ribonucleotide reductase and immunodysfunction in adenosine deaminase deficiency, the effects of deoxyadenosine on ribonucleotide reductase in ADA‐deficient lymphocytes was investigated. An assay system for ribonucleotide reductase in intact permeabilized lymphocytes was developed to approximate physiological conditions. The activity of cytidine diphosphate (CDP) reductase in resting but not in proliferating lymphocytes in culture was inhibited by 1 to 10 µmol/L deoxyadenosine. The resting cells were protected from the toxicity of 1 µmol/L deoxyadenosine by 5 mmol/L nicotinamide or 30 µmol/L deoxycytidine and from that of 10 µmol/L deoxyadenosine by 30 µmol/L deoxycytidine. These findings suggest that depletion of nicotinamide adenine dinucleotide might be the principal cause of death in resting lymphocytes with ADA deficiency. It is concluded that the mechanism of deoxyadenosine toxicity on non‐replicating lymphocytes, which may not be mediated by ribonucleotide reductase inhibition, is closely related to the mechanism of immunodysfunction in patients with ADA deficiency.
Demonstration of 4‐Aminobutyric acid aminotransferase deficiency in lymphocytes and lymphoblasts
Authors: Gibson K. M. , Sweetman L. , Nyhan W. L. , Jansen I. , Jaeken J. 
Published: June 2005

AbstractLysates of lymphocytes, isolated from whole blood, and Epstein‐Barr virus transformed cultured lymphoblasts catalysed the transamination of 4‐aminobutyric acid with 2‐oxoglutaric acid as co‐substrate. 4‐Aminobutyric acid aminotransferase activity in lymphocyte and lymphoblast sonicates derived from 12 unrelated control individuals (6 each) was 39 ± 19 pmol min−1 (mg protein−1) (mean ± 1 SD). Activities in lysates of both types of cell derived from a Flemish patient were less than 3% of control. 4‐Aminobutyric acid aminotransferase activity in sonicates derived from the parents and a healthy sibling were 15–37% of the control mean for lymphocytes and 13–20% of the control mean in lymphoblasts, respectively.Km values in a control lymphoblast sonicate were 0.63 and 0.08 mmol L−1 for 4‐aminobutyric and 2‐oxoglutaric acids, respectively. These data indicate that the parents and healthy sibling are heterozygous and the patient is homozygous for a defective gene responsible for 4‐aminobutyric acid aminotransferase deficiency, and that inheritance is autosomal recessive.
EEG findings as an aid to the diagnosis of neonatal non‐ketotic hyperglycinaemia
Authors: Mises J. , Moussali‐Salefranques F. , Laroque M. L. , Ogier H. , Coude F. X. , Charpentier C. , Saudubray J. M. 
Published: June 2005

AbstractThe periodic EEG pattern during the first week associated with lethargy and myoclonic jerks is the major clinical sign in non‐ketotic hyperglycinaemia. The blood and urine glycine level may be at the upper limit of the normal range in some cases. Diagnosis must be done with this characteristic clinical picture associated with a high CSF glycine level.
Molecular basis of ornithine transcarbamylase deficiency lacking enzyme protein
Authors: Saheki T. , Imamura Y. , Inoue I. , Miura S. , Mori M. , Ohtake A. , Tatibana M. , Katsumata N. , Ohno T. 
Published: June 2005

AbstractWe report an ornithine transcarbamylase(OTC)‐deficient male patient who had no detectable immunoreactive materials but did have active mRNA for OTC‐related protein. The total absence of OTC activity in the liver of the patient was caused by a complete lack of immunoreactive material, as determined by Ouchterlony double immunodiffusion, single radial immunodiffusion, and sodium dodecylsulphate‐polyacrylamide gel electrophoresis of immunoprecipitate and of liver homogenate.However, mRNA coding for the precursor of OTC was clearly detected in autopsy specimens of the patient's liver as well as of controls in a cell‐free translation system consisting of rabbit reticulocyte lysates and [35S]methionine. The labelled precursor of OTC synthesizedin vitro with mRNA from the patient could be transported into rat liver and kidney mitochondria and processed to form a protein with a mulecular weight indistinguishable from mature OTC, suggesting that there was no defect in the protein structure necessary for its transport into mitochondria. These results suggest that the primary defect of the OTC deficiency was located in the structural gene and that the labile OTC‐related protein, after being synthesized with its mRNA, was degraded too rapidly to be detected by the method used.
Familial hyperlysinaemia due to L‐lysineα‐ketoglutarate reductase deficiency: Results of attempted treatment
Authors: v. d. Heiden C. , Brink M. , de Bree P. K. , v. Sprang F. J. , Wadman S. K. , de Pater J. M. , van Biervliet J. P. G. M. 
Published: June 2005

AbstractA mentally retarded male infant with persistent hyperlysinaemia due to L‐lysineα‐ketoglutarate reductase deficiency is described. The effect of dietary restriction of lysine on his mental and behavioural development was examined.By restricting daily dietary lysine to 5.5 mg/kg body weight the fasting serum lysine became normal. Urinary lysine also became normal and the secondary metabolites homocitrulline, homoarginine,Nα‐acetyllysine andNε‐acetyllysine were no longer detected. After control of serum lysine for 2.5y it was felt that the patient's social behaviour, but not his mental development, had improved somewhat.
In vivostudies on the metabolic derangement in a patient with D‐glyceric acidaemia and hyperglycinaemia
Authors: Kølvraa S. , Gregersen N. , Christensen E. 
Published: June 2005

AbstractIn a mentally retarded boy, who excreted elevated amounts of glycine,d‐glyceric acid and acylglycines and whose cells exhibited diminishedd‐glycerate dehydrogenase and glycine cleavage activity, investigations have been undertaken aiming at characterizing the relationship betwnen the different accumulations. This was donein vivoby trying in a specific manner to alter in turn the degree of accumulation of each of the three classes of compounds and then monitoring changes in the others. The results suggest, that thed‐glyceric acid accumulation is directly caused by the genetic defect, since thed‐glyceric acid excretion was not altered by changes in degree of accumulation of either glycine or acylglycines. Similarly alterations in acylglycine excretion caused alterations in glycine but not ind‐glyceric acid excretion.Based on these findings a model for the pathogenesis behind the accumulations of acylglycines and glycine is proposed.
Treatment of thecbl B form of methylmalonic acidaemia with adenosylcobalamin
Authors: Batshaw M. L. , Thomas G. H. , Cohen S. R. , Matalon R. , Mahoney M. J. 
Published: June 2005

AbstractA 30‐month‐old girl was found to have thecbl B mutant form of methylmalonic aciduria by complementation analysis of fibroblasts. She was unresponsive to hydroxycobalamin and was treated with intramuscular adenosylcobalamin (AdoCbl), the deficient coenzyme, at a dose of 1 mg/24 h during a period of clinical stability. Serum cobalamin increased from 770 to 54 200 pg/ml. Mean urinary methylmalonic acid excretion was 409 mg/24 h prior to therapy. There was a transient fall in methylmalonic acid excretion during the first 5 days of therapy (range 167–245 mg/24 h) followed by a rise in excretion toward pretreatment levels (range 317–485 mg/24 h) during the second week of AdoCbl treatment. There was no change in plasma ammonia, glycine or serum bicarbonate level. We interpret the failure of this child to have a sustained and clinically significant response to AdoCbl as indicating that AdoCbl did not reach or enter the mitochondria intact, or in some other way was unavailable as a coenzyme for the methylmalonyl CoA mutase apoenzyme.
β‐Mannosidosis: Prenatal biochemical and morphological characteristics
Authors: Jones M. Z. , Rathke E. J. S. , Cavanagh K. , Hancock L. W. 
Published: June 2005

AbstractCaprine β‐mannosidosis, an autosomal recessive disorder of glycoprotein catabolism, as yet undetected in man, was expressed in a 96/150 day gestation goat fetus. Deficiency of plasma, kidney, brain, liver and skin fibroblast acidic β‐mannosidase activity was associated witht he accumulation of tissue oligosaccharides. Characteristic lucent cytoplasmic lysosomal storage vacuoles were present in the brain, thyroid, kidney and other tissues. Axonal spheroids were present in the central nervous system. The biochemical and morphological prenatal expressions of β‐mannosidosis which were documented by this investigation may facilitate the identification of the disease in man.
Results of a study to detect the effects on neonates of copper and zinc deficiency during pregnancy
Authors: Favier A. , Ruffieux D. , Decoux G. , Arnaud J. 
Published: June 2005

ConclusionOur study shows a link between malformation and zinc deficiency in mother, or copper deficiency in newborn, but this is not a direct relationship to levels under a certain limit. We know that the level of copper or zinc in serum is not a good index of trace element deficiencies, and is disturbed by hormonal changes. Zinc deficiencies may thus be transitory and the first months of pregnancy are most dangerous. Unfortunately in our study we would not have detected such a deficiency at the beginning of pregnancy.
Zinc metabolism in animals: Pathology, immunology and genetics
Authors: Chesters J. K. 
Published: June 2005

AbstractDeficiency of dietary Zn rapidly reduces both appetite and growth, the latter effect being apparently caused by a failure of cell replication. Diagnosis of presymptomatic Zn deficiency depends largely on estimation of plasma Zn concentration but is complicated by reductions of it during a range of stressful conditions. In the latter cases, the decrease in plasma Zn concentration does not appear to be associated with inadequate Zn intake. Only two genetic defects of Zn metabolism are known in animals. One is associated with lethally inadequate concentrations of Zn in the milk of mice, the other with the A46 trait in Friesian cattle. A46 is a recessively inherited defect of Zn absorption which is lethal in the absence of major Zn supplementation of the diet. The characteristics of the disease are very similar to those of acrodermatitis enteropathica in man.
Absence of hepatic molybdenum cofactor: An inborn error of metabolism leading to a combined deficiency of sulphite oxidase and xanthine dehydrogenase
Authors: Wadman S. K. , Duran M. , Beemer F. A. , Cats B. P. , Johnson J. L. , Rajagopalan K. V. , Saudubray J. M. , Ogier H. , Charpentier C. , Berger R. , Smit G. P. A. , Wilson J. , Krywawych S. 
Published: June 2005

AbstractFive patients with a combined deficiency of xanthine dehydrogenase, sulphite oxidase and, probably, also of aldehyde oxidase are described. This remarkable coincidence of three inborn errors of metabolism in a single individual was demonstrated to result from a deficiency of the ‘molybdenum cofactor’, an essential constituent of all three enzymes. The main biochemical findings in these patients included: hypouricaemia, xanthinuria, an increased excretion of sulphite, thiosulphate andS‐sulphocysteine and a decreased excretion of inorganic sulphate. Plasma molybdenum was normal. The ultimate diagnosis was made by the measurement of ‘molybdenum cofactor’ in a liver biopsy specimen in three out of five patients.The clinical hallmarks in these patients were: feeding difficulties, mental retardation, neurological symptoms, lens dislocation, an abnormal muscle tone, myoclonia and an abnormal physiognomy. The majority of these were already present in the neonatal period. So far, attempts at treatment have been unsuccessful.
Zellweger syndrome: Biochemical procedures in diagnosis, prevention and treatment
Authors: Schutgens R. B. H. , Wanders R. J. A. , Heymans H. S. A. , Schram A. W. , Tager J. M. , Schrakamp G. , van den Bosch H. 
Published: June 2005

AbstractIn patients with cerebro‐hepato‐renal (Zellweger) syndrome, the absence of peroxisomes results in an impairment of metabolic processes in which peroxisomes are normally involved. These include the catabolism of very long chain (>C22) fatty acids, the biosynthesis of ether‐phospholipids and of bile acids, the catabolism of phytanic acid and the catabolism of pipecolic acid. Many diagnostic tests for Zellweger syndrome have become available in recent years. In classic Zellweger syndrome abnormal C27‐bile acids, very long chain fatty acids, dicarboxylic acids and pipecolic acid accumulate in the plasma of the patients. Moreover, depending upon the diet, plasma phytanic acid concentrations may be elevated. In platelets the activity of acyl‐CoA: dihydroxyacetone phosphate acyltransferase is deficient; in erythrocytes from young (<4 months) patients the plasmalogen content of the phospholipids is decreased.In cultured fibroblasts from skin and from chorionic villus and cultured amniotic fluid cells from Zellweger patients the plasmalogen level is lowered; there is a decreased activity of acyl‐CoA: dihydroxyacetone phosphate acyltransferase, alkyl dihydroxyacetonephosphate synthase and phytanic acid oxidase; thede novo biosynthesis of plasmalogens and the peroxisomal β‐oxidation of fatty acids are impaired and the intracellular localization of catalase is abnormal.Dietary treatment of patients with Zellweger syndrome has not so far resulted in an objective clinical improvement. As Zellweger syndrome is usually fatal in early life, prenatal diagnosis of the disease is important.