HYPERMETHIONINEMIA: A METABOLIC DISORDER ASSOCIATED WITH CIRRHOSIS, ISLET CELL HYPERPLASIA, AND RENAL TUBULAR DEGENERATION

Abstract
Three infants in one sibship are described, each of whom died during the third month of life after illnesses characterized by irritability and progressive somnolence, and terminally by a tendency to bleed and hypoglycemia. Each infant had a very peculiar odor for several weeks before death. Autopsy disclosed almost identical pathological changes in each infant, consisting of hepatic cirrhosis, renal tubular dilatation, and pancreatic islet hypertrophy. Biochemical investigation of the third infant demonstrated, besides a generalized aminoaciduria, a very marked elevation of methionine in serum, and a disproportionately high excretion of this amino acid in urine. Normal brain cystathionine concentration, and absence of excessive amounts of homocystine and cystathionine from urine, indicated that the major known pathway of methionine degradation was intact. α-Keto-γ-methiolbutyric acid was found in the infant's urine and may have been responsible for the patient's odor. It is suggested that an alternative pathway of methionine breakdown, in addition to that leading through cystathionine, exists in man, and that an enzymatic block, possibly in the oxidative decarboxylation of the alpha keto acid of methionine, might conceivably have accounted for the disease found in these infants.