Methylmalonic acidemia

What is the cause of methylmalonic acidemia?

Isolated methylmalonic acidemia is caused by changes in one of five genes: MMUT , MMAA , MMAB, MMADHC , or MCEE. Methylmalonic acidemia with homocystinuria is caused by mutations in the MMADHC , LMBRD1 and _ABCD4 _genes. Other forms of methylmalonic acidemia are caused by changes in different genes.

Last updated on 05-01-20

How is methylmalonic acidemia diagnosed?

Methylmalonic acidemia can be diagnosed through newborn screening. Almost every state in the United States screens for this disorder. Additional testing required for diagnosis may include:

  • Biochemical testing for abnormal levels of specific chemicals
  • Testing for responsiveness to vitamin B12
  • Genetic testing for mutations in one of the genes associated with methylmalonic acidemia

Last updated on 05-01-20

How is methylmalonic acidemia inherited?

Methylmalonic acidemia is inherited in an autosomal recessive pattern. People with autosomal recessive conditions inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive disorder typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, each child has a:

  • 25% (1 in 4) chance to have the disorder
  • 50% (1 in 2) chance to be an unaffected carrier like each parent
  • 25% (1 in 4) chance to be unaffected and not be a carrier.

Last updated on 05-01-20

What is the long-term outlook for individuals with methylmalonic acidemia?

The long-term outcome in methylmalonic acidemia varies. The age at which symptoms first occur and the severity of symptoms are different from person to person. In general, early diagnosis and treatment is associated with a better outcome. Some children have life-long learning problems, intellectual disability, seizures, or growth delay, even with treatment. Other possible long-term complications can include vision loss, kidney failure, and liver problems.

Last updated on 05-01-20

How many people have methylmalonic acidemia?

About 1/80,000-1/100,000 babies are born with methylmalonic acidemia worldwide. In the United States, one study estimated that about 1/90,000 babies are born with methylmalonic acidemia.

Last updated on 05-01-20

How might methylmalonic acidemia be treated?

There is no specific treatment for methylmalonic acidemia. Treatment is focused on managing the symptoms. Options include:

  • Aggressive treatment of decompensation events
  • Special protein managed diet
  • Vitamin B12 supplementation for the vitamin B12 responsive subtypes
  • Medications such as carnitine
  • Avoidance of stressors (such as fasting or illness) that can lead to a decompensation event
  • Liver and kidney transplant in some cases

Specialists that may be involved in the care of people with methylmalonic acidemia include:

  • Nutritionist
  • Genetics professional
  • Developmental specialist
  • Neurologist
  • Ophthalmologist
  • Audiologist
  • Nephrologist
  • Physical therapist and occupational therapist

Last updated on 05-01-20

Name: Organic Acidemia Association 9040 Duluth Street
Golden Valley, MN, 55427, United States
Phone: 763-559-1797 Fax : 866-539-4060 Email: Url:
Haijes HA, van Hasselt PM, Jans JJM, Verhoeven-Duif NM. Pathophysiology of propionic and methylmalonic acidemias. Pt 2: Treatment strategies J Inherit Metab Dis. Sept 2019; 42(5). 745-761. Reference Link Haijes HA, Jans JJM, Tas SY, Verhoeven-Duif NM, van Hasselt PM. Pathophysiology of propionic and methylmalonic acidemias. Pt 1: Complications J Inherit Metab Dis. Sept 2019; 42(5). 730-744. Reference Link Zhou X, Cui Y, Han J.. Methylmalonic acidemia: Current status and research priorities Intractable Rare Dis Res. May 2018; 7(2). 73-78. Reference Link Fraser JL, Venditti CP. Methylmalonic and Propionic acidemias: Clinical management and update Curr Opin Pediatr. Dec 2016; 28(6). 682-693. Reference Link Manoli I, Sloan JL, Venditti CP. Isolated Methylmalonic Acidemia GeneReviews. Updated Dec 1, 2016; Reference Link Chace DH1, DiPerna JC, Kalas TA, Johnson RW, Naylor EW.. Rapid diagnosis of methylmalonic and propionic acidemias: quantitative tandem mass spectrometric analysis of propionylcarnitine in filter-paper blood specimens obtained from newborns Clin Chem. Nov 2001; 47(11). 2020-4. Reference Link Sloan JL, Carrillo N, Adams D & Venditti CP. Disorders of Intracellular Cobalamin Metabolism GeneReviews. Updated September 6, 2018; Reference Link Haijes HA, Molema F, Langeveld M, Janssen MC, Bosch AM, van Spronsen F, et al. Retrospective evaluation of the Dutch pre-newborn screening cohort for propionic acidemia and isolated methylmalonic acidemia: What to aim, expect, and evaluate from newborn screening J Inherit Metab Dis. Dec 11, 2019; Epub ahead of print. Reference Link

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