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Genetics of Methylmalonic Acidemia Medication

  • Author: Brendan Lee, MD, PhD; Chief Editor: Maria Descartes, MD  more...
Updated: Mar 16, 2015

Vitamins and cofactors

Class Summary

In patients with cobalamin-responsive methylmalonic acidemia (MMA), cobalamin therapy significantly improves methylmalonyl-CoA mutase activity, to the extent that metabolic control becomes easier and the risk of complications is reduced. Patients with MMA are treated with L-carnitine to remove excess toxic acylcarnitine species from the mitochondria. This detoxification is particularly important at diagnosis and during episodes of metabolic decompensation. If necessary, doses can be increased and/or administered by a parenteral route. Additional nonspecific therapy with betaine and folate potentially reduces plasma homocysteine levels.

Hydroxocobalamin (Cyanokit, Hydro Cobex, Hydro-Crysti-12, LA-12)


DOC in France and Scandinavia. Hydroxocobalamin (vitamin B-12a) is an analog of cyanocobalamin (vitamin B-12). It is more highly protein bound and is retained in the body longer than cyanocobalamin. Combines with cyanide to form nontoxic cyanocobalamin (vitamin B-12). Patients with MMA potentially are responsive to cobalamin. Once patients are diagnosed, administer 1 mg/d hydroxocobalamin IM until complementation analysis confirms the definitive diagnosis.

Levocarnitine (Carnitor)


An amino acid derivative, synthesized from methionine and lysine, required in energy metabolism. Modulates intracellular coenzyme A homeostasis and is required to buffer toxic acyl-CoA compounds within the mitochondria.

Folate (Folvite)


Important cofactor for enzymes used in production of red blood cells.

Betaine (Cystadane)


Methyl group donor in remethylation of homocysteine to methionine. It is available as an orphan drug in the United States.



Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Metronidazole (Flagyl)


Treatment of susceptible bacteria in the lower GI tract reduces propionate production. Propionate is an important precursor of methylmalonic acid. Limited trial (1-2 mo) is warranted when metabolic control is difficult with carnitine, cobalamin, and dietary therapy.

Neomycin PO (Mycifradin)


Inhibits bacterial protein synthesis and growth.

Contributor Information and Disclosures

Brendan Lee, MD, PhD Professor, Robert and Janice McNair Endowed Chair in Molecular and Human Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine

Brendan Lee, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, Society for Pediatric Research

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Biomarin; Retrophin;.


Olaf A Bodamer, MD, PhD, FAAP, FACMG Park Gerald Chair in Genetics and Genomics, Associate Chief, Division of Genetics and Genomics, Department of Medicine, Boston Children's Hospital, Harvard Medical School

Olaf A Bodamer, MD, PhD, FAAP, FACMG is a member of the following medical societies: American Medical Association, American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Christian J Renner, MD Consulting Staff, Department of Pediatrics, University Hospital for Children and Adolescents, Erlangen, Germany

Disclosure: Nothing to disclose.

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