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Biomedical subjects

R J Pollitt

Publications and source records attributed to R J Pollitt.

At least 91 records · Page 5Linked to original sources
PubMed1986

Glutaric aciduria type 1: biochemical investigations and postmortem findings.

Glutaric aciduria type 1 (GA1; deficiency of glutaryl - CoA dehydrogenase) was diagnosed in a 6.5-month-old female infant. Despite a good biochemical response to dietary reduction of lysine and tryptophan, there was no clinical response to diet nor to riboflavin therapy and her neurological condition deteriorated progressively until her death at 10.5 months. At postmortem examination only mild neuropathological abnormalities were found in contrast to previous reports of this condition. High levels of glutarate were found in liver, skeletal muscle, heart muscle and aqueous humor. Eye fluid which is readily available, may be a useful material for the postmortem diagnosis of this, and other organic acidurias when urine is not available.

Brain↗
PubMed1985

Tracer studies of the interconversion of R- and S-methylmalonic semialdehydes in man.

Two human subjects were given separate oral doses of sodium [2H6]isobutyrate and [methyl-2H3]thymine and the labelling patterns of urinary metabolites were determined. Ingestion of deuterated isobutyrate resulted in the excretion of 2H5-labelled S-3-hydroxyisobutyric acid, formed on the direct catabolic pathway, and of S- and R-[2H4]-3-hydroxyisobutyric acids, formed by the reduction of S- and R-methylmalonic semialdehydes respectively. Only the R-enantiomer of urinary 3-hydroxyisobutyric acid was labelled by thymine. This labelling pattern indicates a flow from S- to R-methylmalonic semialdehyde, suggesting that the R-enantiomer is the substrate of methylmalonic semialdehyde dehydrogenase.

Butyrates↗
PubMed1985

Riboflavin-responsive ethylmalonic-adipic aciduria.

A patient presenting with a condition resembling Reye's syndrome was found to have a urinary organic acid excretion pattern similar to those previously described in a single patient with ethylmalonic-adipic aciduria. The present patient responded clinically to riboflavin supplementation and his fibroblasts, when cultured in riboflavin-depleted medium, showed an abnormal reduction in the rate of butyrate oxidation.

Adipates↗
PubMed1985

Excessive excretion of beta-alanine and of 3-hydroxypropionic, R- and S-3-aminoisobutyric, R- and S-3-hydroxyisobutyric and S-2-(hydroxymethyl)butyric acids probably due to a defect in the metabolism of the corresponding malonic semialdehydes.

A new metabolic disorder characterised by the excessive excretion of beta-alanine, 3-hydroxypropionic acid, R- and S-3-amino- and 3-hydroxyisobutyric acids and S-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 both R- and S-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.

Alanine↗
PubMed1984

Glutaric aciduria type II: biochemical investigation and treatment of a child diagnosed prenatally.

Two sibs with the acute neonatal form of glutaric aciduria type II (deficient in vivo activity of multiple acyl-CoA dehydrogenases) are described. In the second case diagnosis was made prenatally on the basis of reduced oxidation of palmitate by cultured amniotic fluid cells. With prompt intervention in the neonatal period and a carefully controlled diet later, this second progressed well up to 4 months of age but died suddenly of cardiac failure, probably attributable to accumulation of fat. Neither patient showed any congenital morphological abnormality. Cultured fibroblasts from the second case showed a marked defect in the oxidation of a range of substrates requiring acyl-CoA dehydrogenases for their catabolism, but residual activity for some substrates was quite high. Large quantities of sarcosine were excreted in urine, again suggesting that the mutation leaves some residual dehydrogenation activity. Butyryl-, octanoyl- and palmitoyl-CoA dehydrogenases were present in essentially normal quantities in postmortem liver.

Adipates↗
PubMed1984

The routine investigation of urinary organic acids in selected paediatric patients: results over a 2 1/2-year period.

Over a 2 1/2-year period 13 patients with inborn errors of organic acid metabolism, excluding undifferentiated lactic acidosis, have been diagnosed in our laboratories. The diagnostic yield in patients who had not previously been investigated by organic acid chromatography was 1 in 25, the majority of cases having presented with metabolic acidosis. A larger number of non-specific abnormalities were also detected. This type of investigation is beset with pitfalls and is extremely labour intensive.

Acidosis↗
PubMed1983

The occurrence of substituted 3-methyl-3-hydroxyglutaric acids in urine in propionic acidaemia and in beta-ketothiolase deficiency.

THe urine of two patients with propionic acidaemia contained 3-ethyl-3-hydroxyglutaric acid which has a propionyl residue in place of one of the acetyl residues of the normal metabolite 3-methyl-3-hydroxyglutaric acid. Related compounds, 2,3-dimethyl-3-hydroxyglutaric acid, 2-methyl-3-ethyl-3-hydroxyglutaric acid and 2,3,4-trimethyl-3-hydroxyglutaric acid, could not be detected in propionic acidaemia urine, but 2,3-dimethyl-3-hydroxyglutaric acid was excreted by a patient with beta-ketothiolase deficiency.

Acetyl-CoA C-Acyltransferase↗
PubMed1983

Studies on the pathway from ornithine to proline in cultured skin fibroblasts with reference to the defect in hyperornithinaemia with hyperammonaemia and homocitrullinuria.

The reduction in the conversion of ornithine to proline by fibroblasts from a patient with hyperornithinaemia with hyperammonaemia and homocitrullinuria cannot be explained by a reduced uptake of exogenous ornithine, an altered total intracellular ornithine content, or reduced conversion of gamma-glutamate semialdehyde to proline. However, neither could the postulated defect in mitochondrial ornithine uptake be demonstrated using the digitonin method. Increasing the ornithine concentration in the medium increased the incorporation of 14C label from ornithine into protein in both the patient's and control cells. In the patient's cells the apparent Km for ornithine was ten times that of the controls, although the Vmax values were comparable. This result parallels the clinical response to ornithine supplementation.

Amino Acid Metabolism, Inborn Errors↗
PubMed1982

Unexplained diarrhoea and failure to thrive in 2 siblings with unusual facies and abnormal scalp hair shafts: a new syndrome.

A family is described in which 2 siblings born to healthy parents presented with abnormal facies, persistent diarrhoea, and early death. Exhaustive pathological and biochemical investigations failed to find a cause. The scalp hair of both babies had an abnormal amino-acid composition, and presented an appearance that was unique on scanning electron microscopical examination; this fact and the clinical picture probably represents a new syndrome.

Amino Acids↗