Friedreich ataxia (OMIM #229300) is characterized by ataxia, cardiomyopathy, and accumulation of iron in mitochondria of the dentate nucleus of the cerebellum and of cardiac myocytes. Systemic iron overload does not occur. This is the most common type of heritable ataxia, and affects approximately 1 person per 30,000.

Clinical manifestations

Initial clinical evidence of Friedreich ataxia usually occurs in adolescents and adults less than 25 years of age. In 115 affected individuals in 90 families, the onset of symptoms occurred at mean age 10.5 years. The symptoms and signs that appear during the first 5 years are ataxia of limbs and trunk, and absence of deep tendon reflexes. As the condtion worsens, additional characteristic findings develop, including dysarthria, hypotonia, scoliosis, a Babinski plantar extensor response, loss of position sense in toes, and loss of vibratory sensation in feet. Peripheral neuropathy adds a sensory component to gait ataxia. Affected individuals experience progressive loss of ability to walk, causing 95% to become chair bound by age 44 years. Pes cavus is common, and is caused by nerve injury and consequent atrophy of intrinsic muscles of the feet.

Hypertrophic cardiomyopathy is present in two-thirds of the patients. This typically affects the interventricular septum or the wall of the left ventricle. In some patients, echocardiography demonstrates cardiac hypertrophy or decreased left ventricular ejection fraction before overt heart failure occurs. Heart failure is the most common cause of death in patients with Friedreich ataxia. Oculomotor abnormalities (nystagmus) develop in some patients.