Isovaleric acidemia, ... syndrome (deficiency isovaleric acid-CoA dehydrogenase; IVD, deficiency ...,) (Isovaleric acidemia syndrome) - IVD Gen
Isovaleric acidemia is a rare condition in which the body is unable to properly metabolize certain proteins. An alteration of organic acids, which makes anormale accumulate in amounts considered. Abnormal levels of organic acids in the blood (organic acidemia) in urine (organic aciduria) and tissues, may be toxic and cause health problems important. The body breaks down food proteins in amino acids, which are used to provide energy. People with isovaleric acidemia have decreased concentrations of enzyme required to decompose the amino acid leucine.
Alterations that occur due to the isovaleric acidemia can be very mild to life threatening. In severe cases, manifestations of isovaleric acidemia manifest within days of birth. Initial symptoms include anorexia, vomiting, convulsions and lethargy. These symptoms may progress to more severe manifestations, such as seizures, coma and even death. A sign of isovaleric acidemia is the characteristic smell of sweaty feet in the acute phase of the disease caused by the accumulation of isovaleric acid. In other cases, the signs and symptoms of isovaleric acidemia appear during childhood and can fade over time. In addition, affected children may have delayed development and growth. In these children, the episodes of the most serious health problems can be triggered by prolonged fasting, infections, or eat as much protein foods. However, there are also cases of people with genetic mutations that cause isovaleric acidemia, who are asymptomatic.
Isovaleric acidemia is caused by the existence of mutations in the IVD gene, located on the long arm of chromosome 15 (15q14-q15). The IVD gene, encoding the enzyme isovaleryl-CoA dehydrogenase that participates in the metabolism of ingested protein, specifically the amino acid leucine, which is part of many of them. This enzyme is found in the mitochondria, where it participates in the third stage of metabolizing leucine. This step is a chemical reaction that converts the molecule isovaleryl-CoA 3-methylcrotonyl-CoA. Other subsequent reactions convert 3-methylcrotonyl-CoA molecules that are used to produce energy.
They have identified at least 29 missense mutations, 1 small deletion and 2 small insertions in the IVD gene in people with isovaleric acidemia. Some of these mutations disrupt the normal function of the enzyme, while others prevent cell have any functional enzyme. As a result, the body is unable to break down leucine correctly, so isovaleric acid and related molecules accumulates, reaching harmful concentrations. This buildup damages the brain and nervous system, leading to serious problems.
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 syndrome isovaleric acidemia, by complete PCR amplification of the exons of the IVD 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).