Childhood - onset spinocerebellar ataxia -IOSCA- (spinocerebellar ataxia Infantile onset -IOSCA-) - Gen C10orf2.
Spinocerebellar ataxia childhood - onset (IOSCA) is a progressive disorder that affects the nervous system. Affected newborns generally develop the disease during the first year of life. Signs and symptoms of the disease become evident in early childhood and those affected may have ataxia, hypotonia, athetosis and decreased reflexes. In adolescence, these individuals require wheelchair.
Often, people with IOSCA develop problems with the autonomic nervous system. As a result, they may have excessive sweating, difficulty controlling urination and severe constipation. Other signs and symptoms of the disease may include impaired vision and hearing, such as ophthalmoplegia, optic atrophy, and sensorineural hearing loss. In addition, these individuals may have epilepsy that can lead to encephalopathy. Most of those affected survive to adulthood. However, some individuals have a particularly severe form of the disease in which liver damage and encephalopathy that develops during early childhood occurs. These children usually do not live beyond 5 years old.
Spinocerebellar ataxia childhood - onset is due to mutations in the gene C10orf2, located on the long arm of chromosome 10 (10q24). This gene encodes two very similar proteins called "Twinkle" and "Twinky" localized in mitochondria. Mitochondria contain mitochondrial DNA (mtDNA), essential to normal function. The "Twinkle" protein is involved in the synthesis and maintenance of mtDNA, functioning as a helicase mitochondrial DNA. The role of "Twinky" protein is unknown.
They have identified at least three mutations in the C10orf2 gene in people with spinocerebellar ataxia childhood - onset (IOSCA). The most common mutation replaces the amino acid tyrosine by the amino acid cysteine at position 508 in the protein Twinkle (Tyr508Cys or Y508C). Mutations in the gene C10orf2 disrupt the function of "Twinkle" and result in reduced amounts of mitochondrial DNA. The deterioration of mitochondrial function, especially in the nervous system (which requires a lot of energy), leading to neurological dysfunction and other problems associated with IOSCA. Most affected individuals have two copies of the mutation of the gene in each cell. At least two mutations have been reported that are unique to certain families. In these cases, affected individuals have a copy of the specific mutation in the family and a copy of the Tyr508Cys mutation in every cell.
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 spinocerebellar ataxia childhood - onset (IOSCA), by complete PCR amplification of the exons of C10orf2 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).