A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 1: Isolated methylmalonic acidemias (MMA)

PURPOSE: Medical foods for methylmalonic and propionic acidemias (MMA/PA) contain minimal valine, isoleucine, methionine and threonine, but have been formulated with increased leucine. We aimed to assess the effects of imbalanced branched-chain amino acid intake on metabolic and growth parameters in a cohort of MMA patients ascertained via a natural history study. METHODS: Cross-sectional anthropometric and body composition measurements were correlated with diet content and disease-related biomarkers in 61 patients with isolated MMA (46 mut, 9 cblA and 6 cblB). RESULTS: Patients with MMA tolerated close to the recommended daily allowance (RDA) of complete protein (mut(0): 99.45 ± 32.05% RDA). However, 85% received medical foods, the protein-equivalent in which often exceeded complete protein intake (35%). Medical food consumption resulted in low plasma valine and isoleucine concentrations, prompting paradoxical supplementation with these propiogenic amino acids. Weight and height–for age Z-scores correlated negatively with the leucine/valine intake ratio (r=−0.453, P=0.014, R(2)=0.209 and r=−0.341, P=0.05, R(2)=0.123, respectively). CONCLUSION: Increased leucine intake in patients with MMA resulted in iatrogenic amino acid deficiencies and was associated with adverse growth outcomes. Medical foods for propionate oxidation disorders need to be redesigned and studied prospectively, to ensure efficacy and safety. TRIAL REGISTRATION: This clinical study is registered in www.clinicaltrials.gov with the ID: NCT00078078. Study URL: http://clinicaltrials.gov/ct2/show/NCT00078078