Abstract
Known inborn errors of metabolism affect 4 different enzymes in the oxidation of isoleucine to succinate. A new disease involves a fifth enzyme responsible for the formation of propionate from α-methylacetoacetate. This compound and its precursor, α-methyl-β-hydorxybutyrate, are not present in significant amounts in body fluids of normal persons. Large amounts were identified by GC and mass spectrometry, at all times in the urine of a boy who experienced 3 episodes of transient but profound metabolic acidosis. Their concentration increased greatly during acute febrile illness and specifically after L-isoleucine loading. Butanone was present on these occasions while levels of amino acids and propionate were normal. The parents and one fo two sibs of the proband constantly excrete modest amounts of the two organic acids, and the latter were increased by isoleucine loading in contrast to the normal response. In vitro oxidation of isoleucine-u-14C by cultured skin fibroblasts incubated at 37C was 40 percent of normal in the proband; there was no further inhibition after 24 hour incubation at 40C. The study of this mutant phenotype confirms that later stages of isoleucine catabolism are analogous to oxidation of straight-chain fatty acids.
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Daum, R., Delvin, E., Goldman, H. et al. A new inherited defect of isoleucine catabolism. Pediatr Res 5, 392 (1971). https://doi.org/10.1203/00006450-197108000-00089
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DOI: https://doi.org/10.1203/00006450-197108000-00089