Biotin-response Organicaciduria: MULTIPLE CARBOXYLASE DEFECTS AND COMPLEMENTATION STUDIES WITH PROPIONICACIDEMIA IN CULTURED FIBROBLASTS

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Abstract

Fibroblast cultures from two individuals with biotin-responsive organicacidemia were found to have a pleiotropic deficiency of propionyl-CoA carboxylase, β-methylcrotonyl-CoA carboxylase, and pyruvate carboxylase activities after growth in biotin limited culture medium, conditions which do not affect the carboxylase activities of normal cells. All three enzyme activities were restored to normal levels after transferring the mutant strains to biotin-rich medium. Both patients excreted abnormal levels of an array of metabolic intermediates, including β-methylcrotonate, β-hydroxyisovalerate, β-hydroxypropionate, and lactate, which reflect metabolic blocks at all three carboxylase sites.

Authors

M. Saunders, L. Sweetman, B. Robinson, K. Roth, R. Cohn, R. A. Gravel