|http://ghr.nlm.nih.gov/ A service of the U.S. National Library of Medicine®|
The official name of this gene is “methylmalonic aciduria (cobalamin deficiency) cblD type, with homocystinuria.”
MMADHC is the gene's official symbol. The MMADHC gene is also known by other names, listed below.
The MMADHC gene provides instructions for making a protein that helps convert vitamin B12 (also called cobalamin) into one of two molecules, adenosylcobalamin (AdoCbl) or methylcobalamin (MeCbl). AdoCbl is required for the normal function of an enzyme known as methylmalonyl CoA mutase. This enzyme helps break down certain protein building blocks (amino acids), fats (lipids), and cholesterol. AdoCbl is called a cofactor because it helps methylmalonyl CoA mutase carry out its function. MeCbl is also a cofactor, but for an enzyme known as methionine synthase. This enzyme converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.
Research indicates that the MMADHC protein may play a role in one of the last steps in AdoCbl and MeCbl formation, the transport of vitamin B12 into mitochondria (specialized structures inside cells that serve as energy-producing centers). Additional chemical reactions then convert vitamin B12 into AdoCbl or MeCbl.
At least four mutations in the MMADHC gene cause a condition called homocystinuria, which is characterized by skeletal problems and intellectual disability. The MMADHC gene mutations that cause homocystinuria result in a protein that cannot produce MeCbl. Without MeCbl, methionine synthase cannot convert homocysteine to methionine. As a result, homocysteine builds up in the bloodstream and methionine is depleted. Some of the excess homocysteine is excreted in urine. Researchers have not determined how altered levels of homocysteine and methionine lead to the health problems associated with homocystinuria.
At least five mutations in the MMADHC gene have been found to cause methylmalonic acidemia, a condition characterized by feeding difficulties, developmental delay, and long-term health problems. The MMADHC gene mutations that cause this condition result in a protein that cannot produce AdoCbl. A lack of AdoCbl impairs the function of methylmalonyl CoA mutase. As a result, certain proteins and lipids are not broken down properly. This defect allows toxic compounds to build up in the body's organs and tissues, causing the signs and symptoms of methylmalonic acidemia.
At least four MMADHC gene mutations can cause methylmalonic acidemia with homocystinuria, a condition that has features of both of the two previously described conditions. People with this combined condition have developmental delay, eye defects, neurological problems, and blood abnormalities. The MMADHC gene mutations that cause this condition result in the production of a protein that cannot produce AdoCbl or MeCbl. Because both of these cofactors are missing, methylmalonyl CoA mutase and methionine synthase do not function normally. Certain proteins and lipids are not broken down and homocysteine cannot be converted to methionine. This dual defect results in a buildup of toxic compounds as well as homocysteine, and a decrease in the production of methionine within the body. This combination of imbalances leads to the signs and symptoms of methylmalonic acidemia with homocystinuria.
Cytogenetic Location: 2q23.2
Molecular Location on chromosome 2: base pairs 149,569,633 to 149,587,816
The MMADHC gene is located on the long (q) arm of chromosome 2 at position 23.2.
More precisely, the MMADHC gene is located from base pair 149,569,633 to base pair 149,587,816 on chromosome 2.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about MMADHC helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
acids ; aciduria ; amino acid ; cholesterol ; CoA ; cobalamin ; cofactor ; deficiency ; depleted ; developmental delay ; disability ; enzyme ; gene ; methionine ; mitochondria ; neurological ; precursor ; protein ; toxic ; vitamin B12
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.