![]() ![]() The management of MMA includes restriction of dietary protein, which is challenging because sufficient essential amino acid (including Val and Ile) intake is needed for optimal growth and must be balanced against the production of “toxic” metabolites derived mainly from propiogenic amino acid oxidation. 6 The management of this group of disorders remains particularly challenging and controversial because, despite early diagnosis by newborn screening and strict adherence to a protein-restricted diet, patients still experience high mortality and morbidity, including recurrent metabolic ketoacidosis and hyperammonemia, growth failure, chronic kidney disease, pancreatitis, and neurologic complications. 6 MUT deficiency leads to impaired metabolism of the BCAAs valine (Val) and isoleucine (Ile), as well as methionine and threonine, odd-chain fatty acids, and cholesterol, all of which depend on MUT activity to isomerize succinyl-CoA at the terminal step of propionyl-CoA metabolism into the Krebs cycle. This group of inborn errors of metabolism results from deficiency of the methylmalonyl-coenzyme A (CoA) mutase (MUT) enzyme ( mut 0 and mut −, caused by complete or partial MUT deficiency) or related disorders ( cblA, cblB, cblD variant 2) that affect the synthesis and transport of the cofactor of the MUT enzyme, 5′-deoxyadenosyl-cobalamin. It is recognized that except for phenylketonuria, for which medical foods have proven critical in improving disease outcomes, studies of the composition and efficacy of other special formulas remain sparse, 2, 3 yet their implementation has emerged as a cornerstone of therapy for many inborn errors of metabolism detected through newborn screening, including the hereditary isolated methylmalonic acidemias (MMAs). Despite the inherent risk of inducing iatrogenic side effects, such products are currently classified as “foods for special dietary use” and therefore excluded from the regulatory requirements that apply to drugs ((37 FR 18229–30, 1972 and 21 U.S.C.360ee (b) (3)). When the underlying defect involves the metabolism of essential nutrients, such as branched-chain amino acids (BCAAs), however, harmful deficiencies can arise if medical foods are used as a primary dietary source. 1 These products are designed to abrogate the accumulation of toxic metabolites by limiting the amounts of precursors metabolized through a disease-specific enzymatic block. Medical foods are specially formulated products intended to provide safe alternatives to a regular diet in patients with inborn errors of metabolism. Medical foods for propionate oxidation disorders need to be redesigned and studied prospectively to ensure efficacy and safety. Increased leucine intake in patients with MMA resulted in iatrogenic amino acid deficiencies and was associated with adverse growth outcomes. ![]() Weight- and height-for-age z-scores correlated negatively with the leucine-to-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). Medical food consumption resulted in low plasma valine and isoleucine concentrations, prompting paradoxical supplementation with these propiogenic amino acids. However, 85% received medical foods, in which the protein equivalent often exceeded complete protein intake (35%). Patients with MMA tolerated close to the recommended daily allowance (RDA) of complete protein ( mut 0: 99.45 ± 32.05% RDA). Methods:Ĭross-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). We aimed to assess the effects of imbalanced branched-chain amino acid intake on metabolic and growth parameters in a cohort of patients with MMA ascertained via a natural history study. Medical foods for methylmalonic acidemias (MMAs) and propionic acidemias contain minimal valine, isoleucine, methionine, and threonine but have been formulated with increased leucine. ![]()
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