Practical management of organic acidemias

Abstract

Organic acidemias or acidurias (OAs) are a group of metabolic disorders which result in organic acids detected in the urine (or plasma). They include the systemic OAs, the cerebral OAs, and the ketogenic/ketolytic OAs. In general, all types of OA can be treated using a similar conceptual organization. The goals of therapy (acute and chronic) include reversal/prevention of catabolism, limitation of non-tolerated precursors, scavenging of toxic intermediates, replacement of the deficient product, use of cofactors when able and treatment of complications using standard methods. In the future, this framework will also include replacement of dysfunctional enzyme with a functional one. Here we review how this conceptional framework applies to the systemic OAs (propionic acidemia, methylmalonic aciduria without homocystinuria, and isovaleric acidemia), the cerebral OA (glutaric aciduria 1) and the ketogenic/ketolytic OA (HMG-CoA lyase deficiency). We review the current recommendations and use examples of how to use this conceptional framework.