A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 1: isolated methylmalonic acidemias.
OBJECTIVE
Medical foods for methylmalonic acidemias (MMAs) and propionic acidemias 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 patients with MMA 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, in which the protein equivalent 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-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).


CONCLUSIONS
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.Genet Med 18 4, 386-395.
Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Irini
http://orcid.org/0000-0003-1543-2941
I
Manoli
Nutrition Department, National Institutes of Health, Bethesda, Maryland, USA.
Jennifer G
http://orcid.org/0000-0001-7683-2557
JG
Myles
Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Jennifer L
http://orcid.org/0000-0003-4520-0949
JL
Sloan
Division of Genetics, Stead Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
Oleg A
OA
Shchelochkov
Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Charles P
CP
Venditti
D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000178:diet therapy*; D000597:Amino Acids, Branched-Chain; D001823:Body Composition; D001837:Body Weights and Measures; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004032:Diet / Q000009:adverse effects; D004044:Dietary Proteins; D019587:Dietary Supplements; D019468:Disease Management; D005260:Female; D006801:Humans; D008297:Male; D016896:Treatment Outcome; D055815:Young Adult
D000597:Amino Acids, Branched-Chain; D004044:Dietary Proteins