A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 2: Cobalamin C deficiency (cblC).()

PURPOSE: Cobalamin C (cblC) deficiency impairs the biosynthesis of adenosyl- and methylcobalamin 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 patients. METHODS: Dietary intake was correlated with biochemical, anthropometric, body composition measurements and other disease parameters in a cohort of 28 early-onset cblC patients. RESULTS: Protein restricted diets were followed by 21% of the patients, while 32% received medical foods. Patients on protein-restricted diets had lower height-for-age Z-score (P=0.034), while 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 of diagnosis, a history of seizures and the leucine/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. TRIAL REGISTRATION: This clinical study is registered in www.clinicaltrials.gov with the ID: NCT00078078. Study URL: http://clinicaltrials.gov/ct2/show/NCT00078078