Search PubMed⌕ Search

Biomedical subjects

S K Wadman

Publications and source records attributed to S K Wadman.

At least 73 records · Page 4Linked to original sources
PubMed1984

The differential diagnosis of dicarboxylic aciduria.

Various types of dicarboxylic aciduria are known, most of them are accompanied by non-ketotic hypoglycaemia. For the differential diagnosis of these conditions several methods of investigation have been used: (1) analysis of urinary organic acids in both native and hydrolysed samples, (2) analysis of free and esterified carnitine, the latter by means of chromatographic separation and identification of acyl moieties, (3) analysis of plasma organic acids, including the so-called free fatty acids, (4) a prolonged fasting test with serial measurements of the aforementioned parameters and close monitoring of the blood glucose and (5) an oral loading test with medium chain triglycerides accompanied by the same measurements as those named in item (4). So far differentiation has been made between patients with a metabolite profile most probably characteristic of medium chain acyl-CoA dehydrogenase deficiency and other dicarboxylic acidurias, among the latter systemic carnitine deficiency. Patients belonging to the first group accumulate octanoate, decanoate and cis-4-decenoate in their plasma; they excrete hexanoylglycine, octanoylcarnitine and suberylglycine in addition to the usual C6-C10 dicarboxylic acids. There was a high prevalence of an increased plasma free fatty acid/3-hydroxybutyrate ratio.

Acyl-CoA Dehydrogenase↗
PubMed1984

Occurrences of methylmalonic aciduria and Hartnup disorder in the same family.

Methylmalonic aciduria and Hartnup disorder are two rare autosomal recessively inherited metabolic disorders. We have described the coexistence of these disorders within the same pedigree in two unrelated families. This association was not found in 57 other families surveyed because of a proband known to have either methylmalonic aciduria or Hartnup disorder.

Adult↗
PubMed1984

Identification of methyl-branched chain dicarboxylic acids in amniotic fluid and urine in propionic and methylmalonic acidemia.

3-Methyladipic, 4-methylpimelic, 4-methylsuberic, pimelic, and azeleic acids were identified by gas chromatography-mass spectrometry in the amniotic fluid of fetuses with propionic acidemia. These compounds were virtually undetectable in normal amniotic fluid. Concentrations much higher than those of the amniotic fluid were found in the urine of neonatal infants with propionic acidemia and methylmalonic acidemia. It appears that the accumulation of these compounds is a consequence of the accumulation of propionyl-CoA. Evidence was obtained for the presence of other methyl-branched chain dicarboxylic acids. 4-Methylpimelic acid and 4-methylsuberic acid have not previously been identified in human physiological fluids.

Amniotic Fluid↗
PubMed1984

The effect of deoxyguanosine on human lymphocyte function. I. Analysis of the interference with lymphocyte proliferation in vitro.

The effect of deoxyguanosine on mitogen- and antigen-induced proliferation of peripheral blood lymphocytes from healthy donors was studied. Deoxyguanosine was found to inhibit the proliferative response to mitogens and antigens. Concentrations of deoxyguanosine causing 50% inhibition of the proliferation proved to be dependent on the activity of catabolic enzymes, such as purine nucleoside phosphorylase (PNP), in sera used in the culture media. The inhibitory effect of deoxyguanosine on phytohemagglutinin (PHA)-induced cell proliferation was prevented by deoxycytidine as well as by hypoxanthine. These findings were analyzed further by determination of intracellular (deoxy)-nucleotide levels. Stimulation of lymphocytes by PHA in the presence of deoxyguanosine leads to intracellular accumulation of dGTP. The presence of hypoxanthine in addition to deoxyguanosine abolished the inhibitory effect but did not prevent dGTP accumulation. On the other hand, the addition of deoxycytidine in combination with deoxyguanosine did not lead to intracellular accumulation of detectable amounts of dGTP, but only gave partial protection against the toxic effect. Furthermore, guanosine inhibited mitogen-induced cell proliferation to the same extent as did deoxyguanosine provided that the culture media were supplemented with pretreated fetal calf serum. Peripheral blood lymphocytes of a PNP-deficient or a HGPRT-deficient patient in cultures stimulated with PHA or pokeweed mitogen were resistant to the inhibitory effects of guanosine and were less sensitive to deoxyguanosine than cells of normal donors. The present results clearly show the involvement of two pathways contributing to deoxyguanosine-mediated inhibition of the proliferation of normal lymphocytes, i.e., on the one hand degradation of deoxyguanosine by PNP, salvage of guanine by HGPRT, and (possibly) phosphorylation of GMP eventually leading to GTP, and on the other hand formation of dGTP by direct phosphorylation of deoxyguanosine by deoxycytidine kinase.

Deoxycytidine↗
PubMed1983

Isovalerylglucuronide, a new urinary metabolite in isovaleric acidemia. Identification problems due to rearrangement reactions.

Isovaleryl-beta-D-glucuronide, a new metabolite in the urine of patients with isovaleric acidemia, is described. Its gas chromatographic and mass spectrometric parameters are presented. In alkaline solution this glucuronide exhibited intramolecular rearrangements, resulting in isomers bearing the acyl moiety on C-2, C-3 and C-4. The isomers showed similar mass spectra but different positions on the gas chromatogram. In the index patient isovalerylglucuronide was a main metabolite, but the excretion was a transient phenomenon. Only traces of isovalerylglucuronide could also be detected in the urine of three other patients with isovaleric acidemia. The significance of this metabolite for the detoxication of isovalerate in isovaleric acidemia is discussed.

Amino Acid Metabolism, Inborn Errors↗
PubMed1983

Azetidine-2-carboxylic acid contaminated dietary proline as a cause of urinary excretion of 4-amino-2-(S-cysteinyl)butyric acid in patients on oral treatment with a synthetic diet.

Three children with branched-chain ketoaciduria (maple syrup urine disease) were found to excrete an abnormal amino acid when they were on an artificial diet. This substance was identified as 4-amino-2-(S-cysteinyl)butyric acid with the use of column liquid chromatography, gas chromatography--mass spectrometry of various derivatives, and 360 MHz 1H-NMR spectroscopy. The same compound was detected in urine samples from subjects undergoing an oral loading test with L-proline. The chromatographic analysis of commercial proline from two sources indicated that one of the batches was contaminated (less than 1%) with L-azetidine-2-carboxylic acid (the homologue of proline with a four-membered ring). The latter compound is probably metabolized by the human via ring-opening and addition of a cysteine moiety. It is highly probable that the artificial diet given to the patients contained the impure proline and that the L-azetidine-2-carboxylic acid in the proline gave rise to the excretion of the 4-amino-2-(S-cysteinyl)butyric acid.

Azetidinecarboxylic Acid↗
PubMed1983

[Isovaleric aciduria].

Explore the source record for details and available documents.

Amino Acid Metabolism, Inborn Errors↗
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↗
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↗