Medical nutrition therapy in patients with HIBCH and ECHS1 defects: Clinical and biochemical response to low valine diet

Abstract

3-hydroxyisobutyryl-CoA hydrolase (HIBCH) and short-chain enoyl-CoA hydratase (ECHS1 or crotonase) deficiencies are rare disorders in valine catabolism. HIBCH is responsible for the conversion of 3-OH-isobutyryl-CoA to 3-OH-isobutyric acid and its deficiency results in the buildup of 3-OH-isobutyric acid, which conjugates with free carnitine to 3-OH-isobutyryl carnitine (C4OH), which can be detected in acylcarnitine analysis. The ECHS1 enzyme is reversible which results in the buildup of methacrylyl-CoA, a highly reactive compound which conjugates with thiol groups and results in the accumulation of several toxic intermediates, including S-(2-carboxypropyl)-cysteamine, S-(2-carboxypropyl)-cysteine (SCPC) and its carnitine ester (SCPC-C) (Fig. 1) [1]. Open in a separate window Fig. 1 Pathway of valine catabolism. Solid lines denote the metabolic blocks. Solid arrows highlight accumulated metabolites. Dotted arrow shows inhibition of secondary pathways.