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Biomedical subjects

E R McCabe

Publications and source records attributed to E R McCabe.

At least 145 records · Page 8Linked to original sources
PubMed1983

Human glycerol kinase: comparison of properties from fibroblasts and liver.

Kinetic differences in the glycerol kinase activities from human liver and fibroblasts have been previously demonstrated by this laboratory. The present study was undertaken to characterize these enzymatic activities more completely. The pH profiles were similar for the hepatic and fibroblast activities, but the stability of hepatic glycerol kinase varied much more markedly with pH than the fibroblast activity. Subcellular distribution of this enzymatic activity was quite different for liver and fibroblasts, as was the electrophoretic mobility of these activities on polyacrylamide gels. While these data do not distinguish between tissue specific isozymic forms or post-transcriptional modification, hepatic and fibroblast activities are altered similarly in patients with an inherited deficiency of glycerol kinase.

Electrophoresis, Polyacrylamide Gel↗
PubMed1983

Human glycerol kinase deficiency: an inborn error of compartmental metabolism.

Twelve individuals have been described with glycerol kinase deficiency. Five of these individuals are adults who were noted incidentally to have pseudohypertriglyceridemia. Six of these individuals are children who manifest a clinical complex which includes adrenal hypoplasia/insufficiency and developmental delay. Another child has intermittent coma, a normal IQ, and no evidence of adrenal insufficiency. Genetic and biochemical hypotheses are proposed to explain this clinical variability. Glycerol kinase binds specifically and reversibly to the porin, the pore-forming protein of the outer mitochondrial membrane, which also binds hexokinase. Mutations affecting any component of this kinase-binding system will alter the properties of this system. Glycerol kinase deficiency, as an inborn error of this compartmented metabolic system, offers an investigational opportunity for studying this microenvironment.

Adrenal Insufficiency↗
PubMed1983

Newborn screening for phenylketonuria: predictive validity as a function of age.

Data from questionnaires were assembled for 109 infants with phenylketonuria (PKU) and 114 control infants to assess the predictive validity of newborn screening for PKU as a function of age. Patients with PKU had values of less than 4 mg/dL in cord blood and in samples from days 1, 2, and 4 through 7. The proportion of patients with PKU expected to fall below screening cutoffs of 2, 4, and 6 mg/dL was predicted for each age range. Using a cutoff of 4 mg/dL, approximately one third of patients with PKU would be missed by a sample taken from the neonate in the first 12 hours of life, and nearly 10% would be missed with a sample from the second 12 hours of life. This study shows that not all patients with PKU will be detected by newborn screening, and that the phenomenon of early nursery discharges must be considered in developing appropriate screening strategies.

Age Factors↗
PubMed1982

Zinc status and growth of children undergoing treatment for phenylketonuria.

Children 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 micrograms/dl. The mean (+/- SE) hair zinc concentration was 70.2 +/- 11.5 micrograms/g. The mean plasma and hair zinc concentrations of the PKU population were significantly different (p less than 0.05) when compared with mean (+/- SE) normal values of 84.2 +/- 2.9 micrograms/dl and 130.7 +/- 8.3 micrograms/g, respectively. The mean (+/- SD) dietary zinc intake of 10 PKU patients was 8.56 +/- 2.68 mg/day. No significant differences (p less than 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.

Child↗
PubMed1982

Human glycerol kinase deficiency: enzyme kinetics and fibroblast hybridization.

Glycerol kinase deficiency has been associated with neuromuscular, skeletal and adrenal abnormalities and has also been seen in individuals without these clinical findings. Examination of residual enzyme activity in patients' liver, kidney, leukocytes and fibroblasts showed a generalized, heritable defect: the apparent Km for glycerol was increased 5-200-fold over control values, whereas the apparent Km for ATP was not significantly altered. This kinetic defect was similar in fibroblasts from clinically different individuals with this inborn error of metabolism. Hybridization of fibroblasts from these individuals showed no evidence of complementation for glycerol kinase activity.

Adenosine Triphosphate↗
PubMed1980

Glycerol kinase deficiency with neuromuscular, skeletal, and adrenal abnormalities.

Two brothers with a recently described inborn error of metabolism characterized by glyceroluria, hyperglycerolemia, and generalized glycerol kinase deficiency had moderate psychomotor retardation, spasticity, growth failure, a nonspecific myopathy, osteoporosis, and adrenal insufficiency. Glycerol kinase activity in leukocytes and cultured fibroblasts was less than 5% of control values. Hepatic and renal tissue obtained at autopsy in one patient had similarly low enzyme activity. Thus the deficiency of glycerol kinase in these patients appears to be generalized and heritable, though the relationship of the clinical phenotype to the enzymatic defect is not yet established.

Bone and Bones↗
PubMed1980

Multiple acyl-CoA dehydrogenase deficiency (glutaric aciduria type II) with transient hypersarcosinemia and sarcosinuria; possible inherited deficiency of an electron transfer flavoprotein.

When amino acids were infused at a rate of 4 g/kg/day, an infant with hypoglycemia, metabolic acidemia and chronic regurgitation showed hypersarcosinemia and excreted abnormal amounts of sarcosine, isovalerylglycine, isobutyrylglycine, alpha-methylbutyrylglycine, and beta-hydroxyisovaleric, glutaric, alpha-hydroxyglutaric, methylsuccinic, and alpha-hydroxyisobutyric acids in urine. On all other occasions, when protein intake was lower and lipid intake higher, urine organic acids were dominated by methylsuccinic, ethylmalonic, and alpha-hydroxyglutaric acids, and hypersarcosinemia was absent. Autopsy showed severe fatty changes in liver, kidneys, and skeletal muscle. A previous female sibling had died with similar autopsy findings at 4 days of age. While activity of glutaryl-CoA dehydrogenase was completely deficient in liver and almost completely so in kidney, it was normal in cultured fibroblasts in the presence of flavin adenine dinucleotide (FAD) and only marginally low in its absence. Incorporation of D-(2-14C) riboflavin into flavin mononucleotides (FMN) and FAD by kidney tissue was normal. The authors conclude that this disorder is not due to generalized deficiency of glutaryl-CoA dehydrogenase or to a defect in FAD synthesis. The amino and organic acid abnormalities noted are most consistent with a defect in the flavoprotein which transfers electrons from the FAD of sarcosine and acyl-CoA dehydrogenases into the respiratory chain, although a defect in intercompartmental transfer of C4--5 acyl CoA esters across cell membranes is not excluded. The variability of the organic aciduria, which possibly reflects changes in protein and fat intake, suggests that a previous name for this disorder, i.e., glutaric aciduria type II, is inappropriate and should be replaced, perhaps by "multiple acyl-CoA dehydrogenase deficiency."

Acids↗
PubMed1980

Glutaric acidemia: a metabolic disorder causing progressive choreoathetosis.

A boy with glutaric acidemia had psychomotor retardation first noted at age 6 months, recurrent metabolic acidosis, and a progressive quadriparesis with choreoathetosis. He died at age 3 1/2 years. Cultured skin fibroblasts lacked glutaryl-CoA dehydrogenase activity. There was a biochemical, but not a clinical, response to dietary restriction of lysine and tryptophan. The caudate and putamen of the brain showed severe loss of nerve cells and fibers with proliferation of astrocytes, as well as markedly reduced gamma-aminobutyric acid and glutamate decarboxylase activity.

Acidosis↗
PubMed1978

Methylmalonic/beta-hydroxy-n-valeric aciduria due to methylmalonyl-CoA mutase deficiency.

A patient with methylmalonic and beta-hydroxy-n-valeric aciduria, apparently due to deficiency of methylmalonyl-CoA mutase, is described. The excretion of beta-hydroxy-n-valerate did not parallel that of beta-hydroxypropionate and methylmalonate but was observed, together with beta-keto-n-valerate, only during ketosis. beta-Hydroxy-n-valerate excretion thus correlates primarily not with the pool size of propionyl-CoA but with that of acetyl-CoA, and may occur during ketosis in any disorder causing accumulation of propionyl-CoA.

Amino Acid Metabolism, Inborn Errors↗