Glutaric acidemia type II (Glutaric acidemia type II) - Genes ETFa, ETFB and ETFDH.
Glutaric acidemia type II is an inherited disorder that interferes decomposition of protein and fat in the body to produce energy. Proteins and incompletely processed fats can accumulate in the body and cause metabolic acidosis.
This process usually manifests in early childhood as a result of a metabolic crisis, because acidosis and hypoglycemia cause weakness, changes in behavior such as poor diet, decreased activity, and vomiting. These metabolic crisis, which can be potentially lethal, can be caused by common childhood illnesses, or stress situations. In the most severe cases of illness, people may be born with physical abnormalities such as brain malformations, hepatomegaly, dilated cardiomyopathy, fluid - filled cysts and other renal anomalies, unusual facial features and genital abnormalities. Some affected individuals have less severe symptoms and usually manifest later in childhood or adulthood. In milder forms, muscle weakness in adulthood may be the first sign of the disease.
This process is due to mutations in any of the three genes, ETFa, ETFB and ETFDH.
The ETFa genes located on the long arm of chromosome 15 (15q23-q25) and ETFB, located on the long arm of chromosome 19 (19q13.3), encoding the alpha and beta subunits, respectively, which are joined to form an enzyme flavoprotein called the electron transport chain. The ETFDH gene, located on the long arm of chromosome 4 (4q32-q35), encoding the flavoprotein dehydrogenase enzyme involved in the electron transfer chain. These enzymes are active in the mitochondria, and is involved in the process by which the fats and proteins are broken down to produce energy.
Some mutations in either ETFa, ETFB and ETFDH inhibit genes encoding any amount of enzyme. Other mutations result in the coding of a defective enzyme that can not fulfill its role in the breakdown of fats and proteins. This enzyme deficiency causes these nutrients are partially decomposed, accumulate in the body in abnormal concentrations, especially in stressful situations.
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 in IVAMI: in IVAMI perform detection of mutations associated with glutaric acidemia type II, by complete PCR amplification of the exons of ETFa, ETFB and ETFDH genes, respectively, 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).