Methylmalonic acidemia - AbsoluteAstronomy.com

Methylmalonic acidemia (MMA), also called methylmalonic aciduria, is an autosomal recessive

Recessive

In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...

metabolic disorder. It is a classical type of organic acidemia

Organic acidemia

Organic acidemia, also called organic aciduria, is a term used to classify a group of metabolic disorders which disrupt normal amino acid metabolism, particularly branched-chain amino acids, causing a buildup of acids which are usually not present....

.

Methylmalonic acidemia stems from several genotype

Genotype

The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...

s, all forms of the disorder usually diagnosed in the early neonatal period, presenting progressive encephalopathy

Encephalopathy

Encephalopathy means disorder or disease of the brain. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of global brain dysfunction; this syndrome can be caused by many different illnesses.-Terminology:...

, and secondary hyperammonemia

Hyperammonemia

Hyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to encephalopathy and death. It may be primary or secondary....

. The disorder can result in death if undiagnosed or left untreated.

Genetic

The inherited forms of methylmalonic acidemia cause defects in the metabolic pathway where methylmalonyl-coenzyme A (CoA) is converted into succinyl-CoA

Succinyl-CoA

Succinyl-Coenzyme A, abbreviated as Succinyl-CoA or SucCoA, is a combination of succinic acid and coenzyme A.-Source:It is an important intermediate in the citric acid cycle, where it is synthesized from α-Ketoglutarate by α-ketoglutarate dehydrogenase through decarboxylation...

by the enzyme methylmalonyl-CoA mutase

Methylmalonyl-CoA mutase

Methylmalonyl Coenzyme A mutase, also known as MCM is an enzyme that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA and it is involved in key metabolic pathways...

.

Vitamin B₁₂

Vitamin B12

Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...

is also needed for the conversion of methylmalonyl-CoA to Succinyl-CoA. Mutations leading to defects in vitamin B₁₂ metabolism or in its transport frequently result in the development of methylmalonic acidemia.

This disorder has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome

Autosome

An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...

, and two copies of the gene - one from each parent - must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.

Nutritional

A severe nutritional deficiency of vitamin B₁₂ can also result in methylmalonic acidemia. Methylmalonyl CoA requires vitamin B₁₂ to form succinyl-CoA. When the amount of B₁₂ is insufficient for the conversion of cofactor methylmalonyl-CoA into succinyl-CoA, the buildup of unused methylmalonyl-CoA eventually leads to methylmalonic acidemia. This diagnosis is often used as an indicator of vitamin B₁₂ deficiency in serum

Blood test

A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....

Pathogenesis

Methylmalonic acidemia has varying diagnoses, treatment requirements and prognoses, which are determined by the specific genetic mutation causing the inherited form of the disorder. The following are the known genotypes responsible for methylmalonic acidemia:

OMIM	Name	Gene
	cblA type	MMAA MMAA Methylmalonic aciduria type A protein, mitochondrial also known as MMAA is a protein that in humans is encoded by the MMAA gene.-Function:...
	cblB type	MMAB MMAB Cobyrinic acid a,c-diamide adenosyltransferase, mitochondrial is an enzyme that in humans is encoded by the MMAB gene.-External links:* -Further reading:...
	cblC type	MMACHC MMACHC Methylmalonic aciduria and homocystinuria type C protein also known as MMACHC is a protein that in humans is encoded by the MMACHC gene.- Function :...
	cblD type	MMADHC MMADHC Methylmalonic aciduria and homocystinuria type D protein, mitochondrial also known as MMADHC is a protein that in humans is encoded by the MMADHC gene.- Function :...
	cblF type	LMBRD1 LMBRD1 Probable lysosomal cobalamin transporter is a protein that in humans is encoded by the LMBRD1 gene.-External links:*...
	mut type	MUT Methylmalonyl-CoA mutase Methylmalonyl Coenzyme A mutase, also known as MCM is an enzyme that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA and it is involved in key metabolic pathways...

External links

The source of this article is wikipedia, the free encyclopedia. The text of this article is licensed under the GFDL.