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Genetics of Methylmalonic Acidemia Treatment & Management

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

Medical Care

Infants and children with methylmalonic acidemia (MMA) are at increased risk for metabolic decompensation particularly during episodes of increased catabolism (eg, intercurrent infections, trauma, surgery, psychosocial stress). During these episodes, provide treatment that is swift and directed towards reversing catabolism and promoting anabolism.

Limit protein catabolism during acute metabolic crises. Stop usual protein intake and intravenously administer generous fluid and glucose (4-8 mg/kg/min, depending on age) if necessary. Cessation of protein intake should last for no longer than 24 hours.

Continue medication and increase carnitine intake to 200-300 mg/kg/d intravenously if necessary.

Provide appropriate treatment of concurrent illnesses (eg, infections).

Provide early reintroduction of protein intake (within 1-2 d after onset of acute decompensation).

N -carbamyl glutamate (100-250 mg/kg/d) orally can be used to treat hyperammonemia.

Consider hemodialysis or hemofiltration for persistent hyperammonemia and/or metabolic acidosis.


Surgical Care

Several liver and kidney transplantations in infants and children with MMA mut0 have been reported.

Despite apparent corrections of the enzyme defect, children with liver or kidney transplantations continue to excrete MMA. Some of these children also develop a movement disorder.

Consider liver transplantation early in infancy to potentially prevent some of the devastating neurological complications.



Patients require a low-protein diet that provides the minimum natural protein required for growth. Increase dietary protein according to age, weight, and (essential) plasma amino acids levels. Plasma MMA levels may be followed for metabolic control.

Metabolic formula deficient in propiogenic amino acids should be used to provide sufficient protein for growth while limiting whole protein sources to minimize MMA levels.

Avoid long fasts. Provide a late night snack and/or early breakfast to limit the duration of overnight fasting.

Provide calcium and multivitamin supplementation to avoid osteopenia and vitamin deficiency, respectively.



Do not restrict activity.

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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