Recurrent, familial Reye-like syndrome with a new complex amino and organic aciduria

Abstract

Five of 13 siblings from a Jewish-Ashkenazi family suffered from recurrent Reye-like episodes. During attacks, these patients excreted α-keto-adipic, α-hydroxy-adipic, and α-aminoadipic acids, branched-chain keto acids and saccharopine in addition, to lactic, pyruvic, and dicarboxylic acids characteristic of Reye syndrome. The serum concentrations of citrulline and α-aminoadipic acid were elevated and carnitine was at the upper limit of the normal range. Serum acetoacetate level was 4–5 times the β-hydroxybutyrate level, but the pyruvate/lactate ratio was normal. Notably, plasma ketone bodies were lower than expected from the degree of catabolism. When the patients were symptom-free, no abnormal amino or organic acids in serum or urine were detected. These findings might be interpreted as a functional impairment at three different biochemical sites: fatty acid β-oxidation, dehydrogenase complexes of the pyruvic, α-ketoglutaric, α-ketoadipic, and branched-chain keto acids, and pyruvate carboxylase. We suggest that in this hereditary disorder a toxic substance, exogenously or endogenously derived, interfered at multiple sites in different metabolic pathways.