Friedreich's ataxia is an inherited disease that causes progressive damage to the nervous system resulting in symptoms ranging from gait disturbance and speech problems to heart disease. It is named after the German physician Nicholaus Friedreich, who first described the condition in the 1860s. "Ataxia," which refers to coordination problems such as clumsy or awkward movements and unsteadiness, occurs in many different diseases and conditions. The ataxia of Friedreich's ataxia results from the degeneration of nerve tissue in the spinal cord and of nerves that control muscle movement in the arms and legs. The spinal cord becomes thinner and nerve cells lose some of their myelin sheath the insular covering on all nerve cells that helps conduct nerve impulses. The International Statistical Classification of Diseases and Related Health Problems (commonly known by the abbreviation ICD) is a detailed description of known diseases and injuries. ... The following codes are used with International Statistical Classification of Diseases and Related Health Problems. ... The International Statistical Classification of Diseases and Related Health Problems (commonly known by the abbreviation ICD) is a detailed description of known diseases and injuries. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... Ataxia (from Greek ataxiā, meaning failure to put in order) is unsteady and clumsy motion of the limbs or trunk due to a failure of the gross coordination of muscle movements. ...

Friedreich's ataxia, although rare, is the most prevalent inherited ataxia, affecting about 1 in every 50,000 people in the United States. Males and females are affected equally.

Friedreich's ataxia is an autosomal recessive congenital ataxia and is caused by a mutation in Gene X25 that codes for frataxin, located on chromosome 9. This protein is essential in neuronal and muscle cells for proper functioning mitochondria and the mutation causes inadequate production of frataxin. This results in, among other things, a degeneration of nerve tissue in the spinal cord. An autosome is a non-sex chromosome. ... In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ... In biology, mutations are changes to the genetic material (either DNA or RNA). ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Figure 1: A representation of a condensed eukaryotic chromosome, as seen during cell division. ...

Delatycki et al. (2000) provided an overview of the clinical features, pathology, molecular genetics, and possible therapeutic options in Friedreich ataxia. Pathology (from Greek pathos, feeling, pain, suffering; and logos, study of; see also -ology) is the study of the processes underlying disease and other forms of illness, harmful abnormality, or dysfunction. ...

Friedreich's ataxia and muscular dystrophy, though often compared, are completely different diseases. Muscular dystrophy is the result of muscle tissue degeneration whereas Friedreich's ataxia is the result of nervous tissue degeneration caused by a trinucleotide repeat expansion mutation. Both are researched by the Muscular Dystrophy Association. It has been suggested that Congenital muscular dystrophy be merged into this article or section. ... Trinucleotide repeat disorders are due to stretches of DNA in a gene that contain the same trinucleotide sequence repeated many times. ... Muscular Dystrophy Association (MDA) is a U.S. organization founded in 1950 which combats muscular dystrophy and diseases of the nervous system and muscular system in general by funding research, providing medical and community services, and educating health professionals and the general public. ...

There are two types, the classic form and one in association with a genetic vitamin E deficiency. They cannot be distinguished clinically. Tocopherol, or Vitamin E, is a fat-soluble vitamin in eight forms that is an important antioxidant. ...

Symptoms

Symptoms typically begin sometime between the ages of 5 to 15 years, but in Late Onset FA may occur in the 20's or 30's. Symptoms include any combination, but not necessarily all of the following:

• Muscle weakness in the arms and legs
• Loss of coordination
• Vision impairment
• Hearing loss
• Slurred speech
• Curvature of the spine (scoliosis)
• Carbohydrate intolerance
• Extreme heart conditions (e.g., atrial fibrillation, and resultant tachycardia (fast heart rate) and cardiomyopathy (enlargement of the heart))

it presents before 25 years of age with progressive staggering gait, frequent falling and titubation. lowerextremities are more severely involved. Atrial fibrillation (AF or afib) is an abnormal heart rhythm (cardiac arrhythmia) which involves the two small, upper heart chambers (the atria). ... Tachycardia is an abnormally rapid beating of the heart, defined as a resting heart rate of 100 or more beats per minute in an average adult. ...

These symptoms are slow and progressive. Long-term observation shows that many patients reach a plateau in symptoms in the patient's early adulthood. Because of many of these symptoms, a person suffering from Friedrich's Ataxia may require some surgical interventions (mainly for the spine and heart). Often a metal rod is inserted in the spine to help prevent or slow the progression of scoliosis. As progression occurs, assistive devices such as a cane or walker or a wheelchair are required for mobility (independence).

SIGNS

nystagmus, fast saccadic eye movements, truncal titubation, dysarthria, dysmetria, absent deep tendon reflexes, extensor plantar responses, weakness which is greater distally are commonly found.loss of vibratory and proprioceptive sensation occurs. median age of death is 35 years, females have far better prognosis with 20year survival being 100% as compared to 63% in men. cardiac involvement occurs in 90%of patients. cardiomegaly, symmetrical hypertrophy, murmurs, conduction defects. 20% cases are found in association with diabetes mellitus type 1 or 2 or pancreatic β cell dysfunction.

PATHOGENESIS

primary site of pathology is spinal cord and peripheral nerves.sclerosis and degeneration of spinocerebellar tracts, lateral corticospinal tracts, and posterior columns. in peripheral nerves there is a loss of large myelinated fibres.

GENETICS

Classic form has been mapped to 9q13-q21, and mutant gene contains expanded GAA triplet repeats in the first intron of "frataxin gene".

Treatment

Up until recently, possibly due to a lack of understanding of what caused the lack of protein production, treatment has been focused on addressing the symptoms. On August 20th 2006, research findings circulated in Nature Chemical Biology which showed that compounds they developed could reactivate the defective gene in white blood cell samples and restore some level of the protein production. The scientists indicate if progress continues as expected, drugs for human sampling may be available around spring of 2008.

See also

• Ataxia

Ataxia (from Greek ataxiā, meaning failure to put in order) is unsteady and clumsy motion of the limbs or trunk due to a failure of the gross coordination of muscle movements. ...

External links

• NIH Friedreich's Ataxia Fact Sheet
• FARA What is Friedreich's Ataxia?
• Asks the Experts - Responses: Friedreich's Ataxia
• Friedreich's Ataxia Enters 'the Treatment Era'
• Mendelian Inheritance in Man (OMIM) 229300
• NCBI Genes and Disease: Friedreich's ataxia
• GeneReviews: Friedreich ataxia