Methylmalonyl-Coenzyme A mutase deficiency

Title

Other Names:

MCM Deficiency; Vitamin B12-unresponsive methylmalonic acidemia; Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency; MCM Deficiency; Vitamin B12-unresponsive methylmalonic acidemia; Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency; Methylmalonic aciduria, mut TYPE See More

This disease is grouped under:

Methylmalonic acidemia; Methylmalonic acidemia without homocystinuria

Summary 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 delay, intellectual 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]

Last updated: 12/7/2016

Symptoms 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.

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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

Showing of 24 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 10/1/2020

Do you have updated information on this disease? We want to hear from you.

Treatment 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

Last updated: 12/7/2016

Prognosis Prognosis

The threat of metabolic attacks caused by methylmalonyl-Coenzyme A mutase deficieny (MCM deficiency) is lifelong even if the diet is well controlled, but the number and severity of attacks depend on several factors including the amount of working MCM enzyme present and diet. Those with no MCM enzyme (MUT0) have a higher risk of complications and attacks. Those with some working MCM enzyme have less risk of complications, but may still have attacks when ill, stressed, fasting for long periods, or eating too much protein containing the amino acids isoleucine, methionine, threonine and valine.^[1]^[2]^[5]

The life expectancy for people with MCM deficiency has been improving due to early diagnosis and better understanding of dietary requirements and metabolic attack triggers and treatment. Life threatening complications are more common for those with MUT0. However medical researchers are working on several promising treatments.^[1]^[3]^[5]

Last updated: 12/7/2016

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More 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.

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References References

Manoli I, Sloan JL, Venditti CP. Isolated Methylmalonic Acidemia. GeneReviews. January 7, 2016; http://www.ncbi.nlm.nih.gov/books/NBK1231/.
Methylmalonic Acidemia. Genetics Home Reference (NIH - National Institute of Health). July 2011; http://ghr.nlm.nih.gov/condition/methylmalonic-acidemia. Accessed 10/23/2013.
Rosenblaat D and Watkins D. Methylmalonic acidemia with homocystinuria, type cblF. Orphanet. March, 2012; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79284. Accessed 3/5/2014.
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/.
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.
Axenfeld-Rieger syndrome type 2. Online Mendelian Inheritance in Man (OMIM). 2017; http://www.ncbi.nlm.nih.gov/omim/601499.