Deficiency 3-CoA hydratase methylglutaconyl-(3-CoA hydratase methylglutaconyl-deficiency) - Gen AUH.
3-deficiency methylglutaconyl-CoA hydratase is an inherited disease that causes neurological problems. From infancy, children affected manifest psychomotor retardation, speech delay, dystonia and spastic tetraplegia. In addition, affected individuals may also have optic atrophy. In some cases, signs and symptoms of deficiency 3-methylglutaconyl-CoA hydratase begin in adulthood, often around twenty or thirty years old. These individuals have leukoencephalopathy, which probably contributes to dysarthria, ataxia, spasticity, optic atrophy and dementia. Often, affected individuals who show symptoms of the disease in childhood go on to develop leukoencephalopathy and other neurological problems in adulthood.
In all persons deficient 3-CoA hydratase methylglutaconyl-large amounts of 3-methylglutaconic in their body fluids accumulate. This disease is one of a group of metabolic disorders which can be diagnosed by the presence of 3-methyl glutaric urine high concentrations of 3-methylglutaconic aciduria acid.
This process is due to mutations in the AUH gene, located on the long arm of chromosome 9 (9q22.31). This gene encodes methylglutaconyl-3-CoA hydratase enzyme found in mitochondria. Inside of the mitochondria, this enzyme plays an important role in the breakdown of proteins into smaller molecules that cells can be used to produce energy. Specifically, 3-CoA hydratase methylglutaconyl-is responsible for the fifth step in the decomposition of the amino acid leucine. The enzyme converts a molecule called methylglutaconyl-3-CoA 3-hydroxy-3-methylglutaryl-CoA. Furthermore, 3-CoA hydratase methylglutaconyl-also has the ability to bind RNA. Work is to determine the purpose of this RNA binding ability.
They have identified at least 11 mutations in the gene responsible for deficiency AUH 3-CoA hydratase methylglutaconyl-. These genetic changes lead to loss of function of the three-methylglutaconyl-CoA hydratase. No hydratase 3-methylglutaconyl-CoA functional breakdown of leucine is altered. As a result, 3-methylglutaconyl-CoA is diverted to an alternative route and decomposes into multiple acids: 3-methylglutaconic acid, 3-methylglutaric acid and 3-hydroxy-isovaleric acid. These acids accumulate in body fluids, leading to metabolic acidosis and aciduria. Probably an accumulation of these acids in cerebrospinal fluid can damage the brain and spinal cord and contribute to neurological deficiency characteristics of 3-CoA hydratase methylglutaconyl-.
This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with deficiency 3-CoA hydratase methylglutaconyl-by complete PCR amplification of exons AUH gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).