A NEW FORM OF GLUTARIC ACIDEMIA TYPE II (GA2)

Abstract

GA2 may be due to inherited deficiency of electron transfer flavoprotein (ETF) or ETF-ubiquinone oxidoreductase (ETF-QO), proteins that transfer electrons from soluble mitochondrial flavoprotein dehydrogenases to the main respiratory chain. Cell lines from 11 severely affected GA2 infants were assayed for ETF by acy1 CoA:Q1 activity (using purified general acyl CoA dehydrogenase and ETF-QO as electron donor and acceptor), and for ETF-QO by comproportionation of ETF and by NADH:ETF reductase activity.

All but one were deficient in ETF (5 patients; none with anomalies) or ETF-QO (5 patients; all with anomalies). The one that was not was from a girl with nonketotic hypoglycemia, a typical Zellweger facies, normal serum very long chain fatty acids, and glutaric, ethylmalonic, 3-hydroxyisovaleric and isovalerylglycine in urine who died at 6 months of age. Autopsy showed hypertrophic cardiomyopathy, moderate lipid deposition and canalicular stasis in liver, focal glomerular immaturity and cortical cysts in the kidney, and cysts in the cerebral cortex and basal ganglia. Glutaryl CoA dehydrogenase activity in fibroblasts was normal.

This GA2 patient may have a defect in electron transfer between ETF-QO and complex III, and her phenotype may indicate interaction between peroxisomal and mitochondrial compartments.

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