Rare Endocrinology News

Disease Profile

Methylmalonyl-Coenzyme A mutase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

E71.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

MCM Deficiency; Vitamin B12-unresponsive methylmalonic acidemia; Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency;

Summary

Methylmalonyl-Coenzyme A mutase deficiency (MCM deficiency) is a type of methylmalonic acidemia caused by having too little methylmalonyl-CoA mutase. Methylmalonyl-CoA mutase (MCM) is one of the special proteins (enzymes) needed to breakdown certain amino acids found in the food we eat. It is needed to breakdown certain fats too. When the amino acids and fats are not broken down normally, substances which are harmful to the body (including methylmalonic acid) build up and can damage the nervous system, kidneys and other organs. Symptoms of MCM deficiency usually begin in infancy or early childhood and may include tiredness (fatigue), vomiting, dehydration, weak muscle tone (hypotonia), fever, breathing trouble, frequent illnesses and infections, and increased bleeding and bruising. Long term complications include developmental delayintellectual disability, enlarged liver (hepatomegaly), chronic kidney disease, inflammation of the pancreas (pancreatitis), and in severe cases coma and death.[1][2][3][4]

Methylmalonyl-Coenzyme A mutase deficiency (MCM deficiency) is caused by changes or mutations in the MUT gene which can cause no enzyme to be produced (MUT0) or less than normal amounts of the enzyme to be made (MUT-). The more working enzyme that is made, the less severe the symptoms will be.[1][2][3] MCM deficiency is inherited in an autosomal recessive manner. Diagnosis is made based on symptoms, special blood tests and genetic testing.[1][4] Unlike some types of methylmalonic acidurias, B12 supplements are not helpful. Instead treatment includes a special diet low in proteins containing the amino acids isoleucine, methionine, threonine and valine and certain fats but high in calories. Other symptoms are treated as needed.[1][4][5]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
5%-29% of people have these symptoms
Cerebellar hemorrhage
0011695
Percent of people who have these symptoms is not available through HPO
Abnormal globus pallidus morphology
0002453
Autosomal recessive inheritance
0000007
Cardiomyopathy
Disease of the heart muscle
0001638
Coma
0001259
Dehydration
0001944
Delayed CNS myelination
0002188
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Global developmental delay
0001263
Hepatomegaly
Enlarged liver
0002240
Hyperammonemia
High blood ammonia levels
0001987
Hyperglycinemia
Elevated blood glycine levels
0002154
Lethargy
0001254
Leukopenia
Decreased blood leukocyte number
Low white blood cell count

[ more ]

0001882
Metabolic ketoacidosis
0005979
Methylmalonic acidemia
0002912
Methylmalonic aciduria
0012120
Muscular hypotonia
Low or weak muscle tone
0001252
Pancreatitis
Pancreatic inflammation
0001733
Stage 5 chronic kidney disease
0003774
Thrombocytopenia
Low platelet count
0001873
Tubulointerstitial nephritis
0001970
Vomiting
Throwing up
0002013

Treatment

In 2014, guidelines for managment of methylmalonyl-Coenzyme A mutase deficiency (MMC deficiency) were published by professionals across 12 European countries and the United States. These guidelines are based on a review of published medical studies and expert group meetings.[4] The guidelines may be hard to read without a medical background but can be shared with the affected person's doctor or other trusted medical professional: Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Methylmalonyl-Coenzyme A mutase deficiency. Click on the link to view a sample search on this topic.

References

  1. Manoli I, Sloan JL, Venditti CP. Isolated Methylmalonic Acidemia. GeneReviews. January 7, 2016; https://www.ncbi.nlm.nih.gov/books/NBK1231/.
  2. Methylmalonic Acidemia. Genetics Home Reference (NIH National Institute of Health). July 2011; https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia. Accessed 10/23/2013.
  3. Rosenblaat D and Watkins D. Methylmalonic acidemia with homocystinuria, type cblF. Orphanet. March, 2012; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79284. Accessed 3/5/2014.
  4. Baumgartner MR, Hörster F, Dionisi-Vici C, ...and Chakrapani A. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet Journal of Rare Diseases. 2014; 9:130. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180313/.
  5. Mahmud S, Awais Ul Hassan Shah S, and Ali S. Methylmalonic Acidemia. J Coll Physicians Surg Pak. June 2015; 25(6):462-64. https://www.ncbi.nlm.nih.gov/pubmed/26101005.
  6. Axenfeld-Rieger syndrome type 2. Online Mendelian Inheritance in Man (OMIM). 2017; https://www.ncbi.nlm.nih.gov/omim/601499.

Rare Endocrinology News