α-Ketoadipic aciduria: A description of a new metabolic error in lysine-tryptophan degradation

Abstract

Our studies of a mentally retarded male with extremely elevated levels of α-aminoadipic acid and α-ketoadipic acid in his urine have led to the description of a new metabolic defect, a-ketoadipic aciduria. Analysis of the urine and serum from the patient’s family revealed that the patient (KW) had a mentally and physically normal sister (CW) with the same metabolites elevated, but the rest of the family appeared normal. The presence of elevated levels of α-ketoadipate in the urine of the reported sibs suggests a reduced level of α-ketoadipic acid dehydrogenase. This enzyme has not been purified in humans, but is considered to be α-ketoglutaric acid dehydrogenase in several nonhuman animals. We are presenting evidence that would suggest that in humans these may be separate enzymes, or that more than one form of the α-ketoglutaric acid dehydrogenase exists. © 1975 International Pediatric Research Foundation, Inc.