A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 2: cobalamin C deficiency.
OBJECTIVE
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.
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, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Jennifer G
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
Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.|Therapeutics for Rare and Neglected Diseases, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA.
Nuria
N
Carrillo-Carrasco
Tulane University Medical School, New Orleans, Louisiana, USA.
Eva
E
Morava
Clinic for Special Children, Strasburg, Pennsylvania, USA.
Kevin A
KA
Strauss
Clinic for Special Children, Strasburg, Pennsylvania, USA.
Holmes
H
Morton
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 / Q000178:diet therapy* / Q000209:etiology; D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D001823:Body Composition; D001837:Body Weights and Measures; D001921:Brain / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D014806:Vitamin B 12 Deficiency / Q000150:complications / Q000175:diagnosis / Q000178:diet therapy* / Q000378:metabolism; D055815:Young Adult
D000597:Amino Acids, Branched-Chain