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Biomedical subjects

M Duran

Publications and source records attributed to M Duran.

At least 253 records · Page 14Linked to original sources
PubMed1983

Urinary excretion of deuterated metabolites in patients with tyrosinemia type I after oral loading with deuterated L-tyrosine.

1. The metabolic fate of orally given deuterated L-tyrosine, 50 mg/kg body weight, was investigated in seven patients with tyrosinemia type I in order to obtain evidence that the primary defect is at the level of fumarylacetoacetase. 2. The absence of fumarylacetoacetase could be proved in liver biopsy specimens obtained from four patients. 3. All patients excreted deuterated succinylacetoacetate and deuterated succinylacetone was detected in six out of seven. The total amount of these compounds was rather low; maximal 8.3% of the dose. The peak of the excretion occurred 3-6 h after loading, indicating an endogenous formation of the metabolites. 4. All patients excreted deuterated 4-hydroxyphenyl acids, probably reflecting secondary 4-hydroxyphenylpyruvate dioxygenase deficiency connected with liver damage. 5. No evidence for other secondary routes of tyrosine metabolism was found.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed1983

Absence of hepatic molybdenum cofactor: an inborn error of metabolism leading to a combined deficiency of sulphite oxidase and xanthine dehydrogenase.

Five patients with a combined deficiency of xanthine dehydrogenase, sulphite oxidase and, possibly, 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 and S-SUL-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.

Child, Preschool↗
PubMed1983

The urinary excretion of ethylmalonic acid: what level requires further attention?

The urinary excretion of ethylmalonic acid was studied in various patients, including children with glutaric aciduria type II and with beta-ketothiolase deficiency. An increased excretion at a modest level was found in 20 out of 5000 children who were referred for screening of inherited metabolic disease. Two children were studied longitudinally, but no clue to the origin of ethylmalonic acid was found in these cases. It is concluded that follow-up investigation of abnormal ethylmalonic acid excretion is only indicated when additional organic acids such as dicarboxylic acids are excreted in large amounts.

Acetyl-CoA C-Acyltransferase↗
PubMed1983

[A patient with neonatal citrullinemia].

In a four days old neonate, showing feeding difficulties, temperature imbalance, convulsions and coma, citrullinaemia was diagnosed. Subsequent treatment, consisting of protein-restriction, exchange transfusions, arginine suppletion and using an alternative pathway for waste nitrogen excretion (through sodium benzoate administration), resulted in a stable clinical and biochemical condition. Aged ten months, our patient shows a normal growth with psychomotor retardation probably linked with the perinatal events. Because it seems possible nowadays to prolong survival in neonates with inborn errors of urea synthesis, prompt and correct diagnosing of these disease entities becomes urgent in view of the long-term prognosis for the children involved.

Amino Acid Metabolism, Inborn Errors↗
PubMed1982

Organic acidurias: approach, results and clinical relevance.

More than twenty-five inherited organic acidurias have been identified during the last fifteen years. This remarkable development is due mainly to the introduction of gas chromatography, and gas chromatography combined with mass spectrometry, in paediatric laboratories for metabolic disease. The chemical approach is determined mainly by physical properties of the acid, such as their extractability and volatility. Most progress has been made with extractable acids. The techniques used for derivatization are mentioned, such as trimethylsilylation, methylation and the preparation of asymmetric derivatives for the separation of optical enantiomers. Metabolite patterns may be so characteristic that the underlying enzyme defect can be deduced. Examples are the leucine degradation defects, all encountered in the authors' laboratory: branched-chain ketoaciduria; isovaleric acidaemia; 3-methylcrotonylglycinuria; 3-methylglutaconic aciduria; and 3-hydroxy-3-methylglutaric aciduria. These abnormalities are discussed. D-glyceric aciduria is shown as an example of a not yet fully understood organic aciduria. The clinical approach varies. Metabolic acidosis is an indication for organic acid analysis in urine and plasma, but in many defects there is no acidosis, or only a transient one caused by secondary metabolites, such as lactic and 3-hydroxybutyric acids. Gas chromatography is an obligatory routine investigation in screening programmes for inborn errors of metabolism, especially for the examination of acutely ill neonates and premature babies.

Child↗
PubMed1982

The identification of (E)-2-methylglutaconic acid, a new isoleucine metabolite, in the urine of patients with beta-ketothiolase deficiency, propionic acidaemia and methylmalonic acidaemia.

The identification of (E)-2-methylglutaconic acid, a 'new' metabolite of isoleucine, is described. The substance was detected in urine samples from patients with propionic acidaemia, methylmalonic acidaemia and so-called beta-ketothiolase deficiency; in the majority of cases together with N-tiglylglycine. (E)-2-Methylglutaconic acid is thought to be the end product of the 3-methylcrotonyl-CoA carboxylase-catalysed carboxylation of tiglyl-CoA. Prerequisites for the quantitative gas chromatographic analysis of the unstable 2- (and 3-) methyl-glutaconic acid ditrimethylsilyl ester are given.

Acetyl-CoA C-Acyltransferase↗
PubMed1982

Isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency in two sibs.

Two Vietnamese siblings with an isolated deficiency of 3-methylcrotonyl coenzyme A carboxylase in leucocytes and cultured fibroblasts are described. Both children excreted massive amounts of 3-methylcrotonylglycine and 3-hydroxyisovaleric acid. There was no in vivo or in vitro biochemical response to biotin. Apart from an attack of vomiting leading to subcoma in the elder sib four weeks after arrival in the Netherlands, the children were in good health. There were no signs of delayed mental development.

Biotin↗
PubMed1982

Isovaleric acidaemia presenting with dwarfism, cataract and congenital abnormalities.

Isovaleric acidaemia was diagnosed in a 9-year-old girl with an unusual clinical presentation. She was severely mentally retarded, had an extreme growth retardation, bilateral cataracts, multiple fractures of the long bones, vitium cordis and malformations of the head. Frequent infections occurred since early childhood. The relevance of these findings is discussed.

Abnormalities, Multiple↗
PubMed1982

Inherited 3-methylglutaconic aciduria in two brothers--another defect of leucine metabolism.

Two brothers, aged 7 and 5 years, who excreted large amounts of the leucine metabolites 3-methylglutaconic acid, 3-methylglutaric acid, and 3-hydroxyisovaleric acid, are described. The excretion of these metabolites could be enhanced by increasing the leucine intake. Restriction of the protein intake resulted in a marked reduction of the metabolite excretion. However, the excretion of the ultimate leucine metabolite, 3-hydroxy-3-methylglutaric acid, remained unchanged at a low level. The only clinical abnormality was speech retardation. A (partial) deficiency of 3-methylglutaconyl coenzyme A hydratase is proposed to be the most likely underlying defect.

Amino Acid Metabolism, Inborn Errors↗
PubMed1981

Deficiency of fumarylacetoacetase in a patient with hereditary tyrosinemia.

A patient is described with type I tyrosinemia characterized by urinary excretion of succinylacetone together with increased excretion of tyrosine, p-hydroxyphenyllactic, p-hydroxyphenylpyruvic and p-hydroxyphenylacetic acids. Fumarylacetoacetase was measured in a liver biopsy and found to be very low compared to control liver. Furthermore the mass spectra of succinylacetone and fumarylacetoacetate (methoxime-TMS derivatives) are reported. Control jejunal mucosa, leucocytes and fibroblasts showed no enzyme activity; hence the prenatal diagnosis of this disease by measuring the fumarylacetoacetase activity in cultured amniotic fluid cells is not possible at present.

Acetoacetates↗
PubMed1981

2-Mercaptoethanesulfonate-cysteine disulfide excretion following the administration of 2-mercaptoethanesulfonate--a pitfall in the diagnosis of sulfite oxidase deficiency.

In the urine of a neonate with respiratory insufficiency and convulsions a positive sulfite reaction was found, which is suggestive of sulfite oxidase deficiency. The nitroprusside reaction also was positive. More detailed investigations showed that both tests were positive due to the administration of 2-mercaptoethanesulfonate, a mucolytic drug. The patient's urine contained an acidic amino acid with a column chromatographic behaviour like S-sulfocysteine. The high-voltage electrophoretic mobility was slightly different. This compound was isolated from the urine and identified as the mixed disulfide of 2-mercaptoethanesulfonate and cysteine. Its identity was proven with field desorption mass spectrometry, a technique which is suitable for the analysis of sulfonic acid derivatives.

Amino Acids↗
PubMed1981

A case of formiminoglutamic aciduria. Clinical and biochemical studies.

We describe a boy who excreted massive amounts of formiminoglutamic acid and hydantoin-5-propionic acid in his urine. He was mildly mentally retarded and epileptic, whereas his twin-brother was completely normal. Loading with L-histidine enhanced the excretion of both metabolites. Treatment was attempted with high doses of folic acid and methionine, but both were without effect on the excretion levels.

Amino Acid Metabolism, Inborn Errors↗