Effects of medical food leucine content in the management of methylmalonic and propionic acidemias.

Abstract

The current review highlights the varied effects of medical foods high in leucine (Leu) and devoid of valine (Val) and isoleucine (Ile) in the management of methylmalonic acidemia (MMA) and propionic acidemia and cobalamin C (cblC) deficiency, aiming to advance dietary practices. Leu is a key metabolic regulator with a multitude of effects on different organ systems. Recent observational studies have demonstrated that these effects can have unintended consequences in patients with MMA as a result of liberal use of medical foods. The combination of protein restriction and medical food use in MMA and propionic acidemia results in an imbalanced branched-chain amino acid (BCAA) dietary content with a high Leu-to-Val and/or Ile ratio. This leads to decreased plasma levels of Val and Ile and predicts impaired brain uptake of multiple essential amino acids. Decreased transport of methionine (Met) across the blood-brain barrier due to high circulating Leu levels is of particular concern in cblC deficiency in which endogenous Met synthesis is impaired. Investigations into the optimal composition of medical foods for MMA and propionic acidemia, and potential scenarios in which Leu supplementation may be beneficial are needed. Until then, MMA/propionic acidemia medical foods should be used judiciously in the dietary management of these patients and avoided altogether in cblC deficiency.