Abstract
PURPOSE: Cobalamin C (cblC) deficiency impairs the biosynthesis of 5'-deoxyadenosyl-adenosyl- and methyl-cobalamin, resulting in methylmalonic acidemia combined with hyperhomocysteinemia and hypomethioninemia. However, some patients with cblC deficiency are treated with medical foods, devoid of methionine and high in leucine content, that are formulated for patients with isolated propionate oxidative defects. We examined the effects of imbalanced branched-chain amino acid intake on growth outcomes in cblC-deficient patients. METHODS: Dietary intake was correlated with biochemical, anthropometric, and body composition measurements and other disease parameters in a cohort of 28 patients with early-onset cblC deficiency. RESULTS: Protein-restricted diets were followed by 21% of the patients, whereas 32% received medical foods. Patients on protein-restricted diets had lower height-for-age z-score (P = 0.034), whereas patients consuming medical foods had lower head circumference Z-scores (P = 0.037), plasma methionine concentrations (P = 0.001), and predicted methionine influx through the blood-brain barrier Z-score (-1.29 vs. -0.0617; P = 0.007). The combination of age at diagnosis, a history of seizures, and the leucine-to-valine dietary intake ratio best predicted head circumference Z-score based on multiple regression modeling (R(2) = 0.945). CONCLUSIONS: Patients with cblC deficiency treated with medical foods designed for isolated methylmalonic acidemia are at risk for iatrogenic methionine deficiency that could adversely affect brain growth and development.Genet Med 18 4, 396-404.