Classification
There are currently 5 known subgroups of MGA; MGA type I,II,III,IV & V.
| Type | OMIM | Gene | Locus | Also known as/Description | Genetics |
|---|---|---|---|---|---|
| Type I | 250950 | AUH | Chr.9 | 3-Methylglutaconic aciduria type I, 3-Methylglutaconic acidemia or 3-Methylglutaconyl-CoA Hydratase Deficiency | Mutations in the AUH gene cause 3-methylglutaconic aciduria type I. This gene provides instructions for producing 3-methylglutaconyl-CoA hydratase, an enzyme that is involved in processing the amino acid leucine. This amino acid is broken down in the mitochondria during the process of energy production. A deficiency of this enzyme leads to a buildup of 3-methylglutaconic acid, which is eliminated in the urine. Researchers believe that other genes or environmental factors also contribute to the development of this disorder. |
| Type II | 302060 | TAZ | Xq28 | Barth syndrome (BTHS), 3-Methylglutaconic aciduria type II or Cardiomyopathy-neutropenia syndrome | Mutations in the TAZ gene cause 3-methylglutaconic aciduria type II (Barth syndrome). This gene provides instructions for making a protein called tafazzin. This protein plays a critical role in maintaining the levels of a particular lipid, called cardiolipin, located in the inner membrane of the mitochondria. A lack of tafazzin results in abnormalities in the structure and function of mitochondria, leading to the heart defects and other problems seen in this disorder. |
| Type III | 258501 | OPA3 | 19q13.2-q13.3 | 3-Methylglutaconic aciduria type III or Costeff syndrome | Mutations in the OPA3 gene cause 3-methylglutaconic aciduria type III. This gene carries instructions for making a protein that is also found in mitochondria, but whose function is unknown. Researchers have suggested that cells with a defective OPA3 protein are more susceptible to a process that eliminates damaged or unneeded cells (programmed cell death called apoptosis). |
| Type IV | 250951 | ? | ? | 3-Methylglutaconic aciduria type IV | |
| Type V | 610198 | DNAJC19 | 3q26.3 | 3-Methylglutaconic aciduria type V |
The characteristic features of 3-methylglutaconic aciduria type I include speech delay, delayed development of both mental and motor skills (psychomotor delay), elevated levels of acid in the blood and tissues (metabolic acidosis), abnormal muscle tone (dystonia), and spasms and weakness affecting the arms and legs (spastic quadriparesis). Fewer than 20 cases of 3-methylglutaconic aciduria type I have been reported.
Barth syndrome is a common name for 3-methylglutaconic aciduria type II. The main features of Barth syndrome include a weakened and enlarged heart (dilated cardiomyopathy), recurrent infections due to low numbers of white blood cells (neutropenia), skeletal problems, and delayed growth. The incidence of 3-methylglutaconic aciduria type II is approximately 1 in 200,000 male infants.
Costeff optic atrophy syndrome is another name for 3-methylglutaconic aciduria type III. This disorder is characterized mainly by the degeneration of the optic nerves, which carry information from the eyes to the brain. Sometimes other nervous system problems occur, such as an inability to maintain posture, poor muscle tone, the development of certain involuntary movements (extrapyramidal dysfunction), and a general decrease in brain function (cognitive deficit). The incidence of 3-methylglutaconic aciduria type III is about 1 in 10,000 newborns in the Iraqi Jewish population. This disorder is extremely rare in all other populations.
The signs and symptoms of 3-methylglutaconic aciduria type IV are variable and overlap with types I-III. The incidence of 3-methylglutaconic aciduria type IV is unknown.
Read more about this topic: 3-Methylglutaconic Aciduria