Mitochondrial complex II deficiency (Mitochondrial complex II deficiency) - Genes SDHA and SDHAF1.
Deficiency Mitochondrial complex II (MT-C2D) is an alteration of the mitochondrial respiratory chain with heterogeneous clinical manifestations. Complex II deficiency is characterized by a highly variable phenotypic expression. Signs and symptoms of the disease include psychomotor regression in infants, poor growth with lack of speech development, spastic quadriplegia intense, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance and cardiomyopathy. Other signs and symptoms include additional myoclonic seizures and short stature. In general, the onset of the disease is evident in the first year of life. Some patients with mitochondrial complex II deficiency manifest Leigh syndrome or Kearns-Sayre syndrome.
This process is due to mutations in genes SDHA or SDHAF1.
The SDHA gene, located on the short arm of chromosome 5 (5p15), encoding one of the four subunits of the enzyme succinate dehydrogenase (SDH). SDH enzyme plays a critical role in the mitochondria, where the food energy is converted into a form that cells can use. Within the mitochondria, the enzyme SDH joining two important routes in energy conversion: the citric acid cycle (Krebs cycle) and oxidative phosphorylation. As part of the citric acid cycle, the SDH enzyme converts a compound called succinate another compound called fumarate. During this reaction, electrons are released. SDHA active subunit protein is the enzyme that converts succinate, and also helps the electron transfer pathway of oxidative phosphorylation. In oxidative phosphorylation, electrons help create an electrical charge that provides the energy to produce adenosine triphosphate (ATP), the main energy source of the cell. Succinate, the compound in which the enzyme acts SDH, is an oxygen sensor in the cell and can help provide specific pathways that stimulate cells to grow into a low oxygen environment. In particular, succinate stabilizes a protein called hypoxia - inducible factor (HIF) by preventing a reaction would allow HIF decompose. HIF controls several important genes involved in cell division and the formation of new blood vessels in a hypoxic environment. The SDHA gene is a tumor suppressor gene, which means that prevents cells from growing and dividing uncontrollably.
The SDHAF1 gene, located on the long arm of chromosome 19 (19q13.12), encodes a protein found in the mitochondria. Succinate dehydrogenase complex El (SDH) (also known as respiratory complex II) of the mitochondrial respiratory chain consists of four individual subunits. The protein encoded by the gene SDHAF1, is essential for the assembly of SDH.
Homozygous mutations have been identified and heterozygous in the SDHA and SDHAF1 gene. Mutations in the gene SDHA SDHA substituted amino acids in the protein or coding result of an abnormally short protein. These genetic changes alter the activity of the enzyme SDH, impairing the ability of mitochondria to produce energía.Las mutations in the gene cause a deficiency of mitochondrial respiratory chain.
Tests in IVAMI: in IVAMI perform detection of mutations associated with mitochondrial complex II deficiency, by complete PCR amplification of the exons of SDHA and SDHAF1 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).