Glutaric acidemia type I (Glutaric acidemia type I) - Gen GCDH
Glutaric acidaemia type I, also known as glutaric aciduria type I, is a rare genetic disease in which the body can not process certain proteins correctly due to a metabolic disorder which causes a deficiency of the enzyme glutaryl-CoA -deshidrogensasa (GCDH). This enzyme is involved in the metabolism of three amino acids: lysine, and tryptophan hidrolisina. Excessive concentrations of these amino acids and their degradative intermediates can accumulate and cause damage to the brain, particularly in the basal ganglia, which help control movement. It can also cause intellectual disability.
The severity of the disease is highly variable. The disease usually begins to manifest between the first 3-24 months of life, by an acute encephalopathy which causes necrosis in the basal ganglia, the main consequence is an important neurological dysfunction usually involving movement disorders of dystonia type and / or dyskinesia. Macrocephaly is also a common feature, and can be present at birth or develop during the first weeks or months of life. Early detection, prior to the onset of encephalopathy, and initiation of appropriate treatment allow a substantial improvement in the evolution of the disease and, in some cases, the absence of symptoms is achieved without choreoathetosis or dystonia and ratios development within normal limits. By contrast, in those patients in whom the diagnosis and intervention are late, after encephalopathic crisis, is more likely to have persistent neurological involvement.
This process is due to mutations in the gene GCDH, located on the long arm of chromosome 19 (19p13.2). This gene encodes the glutaryl-CoA enzyme deshidrogensasa (GCDH), involved in the processing of the amino acids lysine, and tryptophan hidrolisina, basic components of proteins.
Described over 150 genetic mutations responsible GCDH glutaric acidemia type I. Most of these mutations result in the substitution of an amino acid for another in the enzyme. In the Amish community, all known cases of glutaric acidemia type I derived from the amino acid substitution by alanine amino acid valine at position 421 (A421V or Ala421Val). We found some specific mutations in certain populations of Native Americans. In individuals with glutaric acidemia type I belong to the Lumbee community in North Carolina, it has been found to have a mutation in the amino acid glutamic acid is substituted for lysine at position 414 (Glu414Lys or E414K). Also, a mutation which replaces guanine nucleotide cytosine (IVS1, GT 5) is common in the Ojibwa of Canada 's population.
Mutations in the gene GCDH inhibit coding glutaryl-CoA enzyme deshidrogensasa (GCDH) or result encoding a defective nonfunctional enzyme. This enzyme deficiency allows lysine, and tryptophan and hidrolisina intermediate metabolites accumulate in abnormal levels, particularly at times when the body is under stress. The intermediate metabolites resulting from incomplete transformation of lysine, tryptophan hidrolisina and can harm the brain, including the basal ganglia, leading to the signs and symptoms of glutaric acidaemia type I
This disease is inherited in an autosomal recessive pattern, that is, 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 performed in IVAMI: in IVAMI perform detection of mutations associated with glutaric acidaemia type I, by complete PCR amplification of exons GCDH 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).