FRDA (Friedreich ataxia) - Gen FXN
Friedreich ataxia (FRDA) is a genetic disorder that affects the nervous system and causes movement problems. Symptoms in individuals affected by this disease begin between 5 and 15 years of age, although there are cases below and above this limit, and range from gait disturbances, instability and difficulties in communication, to heart disease fatal. Thus, the degeneration of nerve tissue of the spinal cord and nerves responsible for movement of arms and legs muscles occurs. Thereby progressively thins the spinal cord and nerve cells lose their normal myelin sheath that under normal conditions, allows the transmission of nerve impulses, responsible among other things movement.
Usually, the first symptom is difficulty in the most basic movements like walking. Slowly the disease progresses and expands this difficulty arms and trunk muscles atrophy and some deformities and loss of sensation in the extremities, also susceptible expansion may occur. Heart disease associated with Friedreich's ataxia start from dysarthria, chest pain and palpitations. Heart disease, myocarditis, myocardial fibrosis and heart failure may occur. Some affected individuals develop diabetes, vision problems, hearing loss, or scoliosis.
About 25% of people with Friedreich 's ataxia have an atypical form that begins after 25 years. This type of Friedreich 's ataxia develops between 26 and 39 years old and is known as Friedreich 's ataxia late - onset (LOFA: Late Onset Friedreich Ataxia). When the signs and symptoms begin after 40 disease called Friedreich 's ataxia very late (VLOFA: Very Late Onset FA). VLOFA LOFA and generally progress more slowly than typical Friedreich's ataxia.
The cause of Friedreich ataxia is a mutation in the gene encoding frataxin FXN (frataxin), located on the long arm of chromosome 9 (9q21.11). Frataxin is a protein essential for mitochondrial functioning, since in its absence iron accumulation occurs and, after reaction with oxygen free radicals, causing severe damage, especially nerve and muscle cells. The mutation is exacerbated repeat expansion GAA triplet first intron, that is, while healthy individuals have between 7-22 repetitions, individuals with FRDA have 66-1000 repetitions. When the fault in a noncoding region does not involve the production of proteins altered frataxin, as is usual in other genetic diseases, but generates silencing genome region where it is located and therefore a drastic reduction of frataxin levels. About 2 percent of people with this disease have a GAA trinucleotide repeat expanded in a copy of the FXN gene and other mutation in the other copy of the gene. In most of these cases, the other single nucleotide mutation changes the FXN gene.
Although not entirely clear how mutations in the gene give rise to Friedreich's ataxia, frataxin deficiency seems to reduce the activity of proteins containing iron sulfide groups, which could alter energy production in mitochondria. Cells with insufficient amounts of frataxin are also particularly sensitive to free radicals, which can damage and destroy cells. Thus, the heart, the pancreas and the nervous system are particularly affected by damage accumulation of free radicals. People with GAA segments that are repeated 300 times less tend to have a later onset of symptoms (after 25 years) than those with higher GAA trinucleotide repeats.
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 Friedreich ataxia (FRDA), by complete PCR amplification of the exons of the gene FXN, 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).