The name 3-methylglutaconic aciduria is used to describe five different disorders that impair the functioning of energy-producing centers within cells (mitochondria). As a result of this impairment, pathways that aid in mitochondrial function are disrupted and large amounts of particular acids (3-methylglutaconic acid and 3-methylglutaric acid) build up and are excreted in the urine.
There are five types of 3-methylglutaconic aciduria numbered I, II, III, IV, and V. Types I-III and V are caused by mutations in four different genes and have distinct signs and symptoms. The genetic cause of 3-methylglutaconic aciduria type IV has not been established. The common link among all types of 3-methylglutaconic aciduria is the excretion of large amounts of 3-methylglutaconic acid and 3-methylglutaric acid in the urine.
The features of 3-methylglutaconic aciduria type I include speech delay, delay in the development of 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 of the arms and legs (spastic quadriparesis).
Barth syndrome is the common name for 3-methylglutaconic aciduria type II. The features of Barth syndrome include an enlarged and weakened heart (dilated cardiomyopathy), recurrent infections due to small numbers of white blood cells (neutropenia), weakness in muscles used for movement (skeletal myopathy), and delayed growth.
Costeff optic atrophy syndrome is the common name for 3-methylglutaconic aciduria type III. This disorder is characterized by degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. Other nervous system problems might occur, such as an inability to maintain posture, poor muscle tone, a gradual increase of involuntary jerking movements (choreiform movements), and a general decrease in brain function (cognitive deficit).
The signs and symptoms of 3-methylglutaconic aciduria type IV are variable and overlap with types I-III.
Dilated cardiomyopathy with ataxia (DCMA) is the common name for 3-methylglutaconic aciduria type V. An enlarged and weakened heart (dilated cardiomyopathy) and an inability to coordinate voluntary muscular movements (ataxia) are the hallmark signs of DCMA. The dilated cardiomyopathy usually develops by the age of 3. Some people with DCMA can also have growth failure; mild mental retardation; optic atrophy; and in males, undescended testes (cryptorchidism) and the opening of the urethra on the underside of the penis (hypospadias).