Friedreich Atax..

Genetic disorder characterized by progressive dysfunction of the posterior spinal cord, cerebellum (ataxia, nystagmus), and peripheral nerves. It typically becomes apparent before adolescence. Clinical features include unsteady posture, frequent falling, progressive ataxia, characteristic foot deformities, increasing incoordination of the arms and hands, dysarthria, and nystagmus. It may be associated with cardiomyopathy, chest pain, arrhythmias, and diabetes mellitus. All patients have normal intelligence.

FRDA I; Spinocerebellar Degeneration; Hereditofamilial Spinal Ataxia; Friedreich Tabes.

First described in 1863 by the German neurologist Nicholaus Friedreich.

Degeneration of the posterior spinal column, corticospinal, spinocerebellar, and pyramidal tracts. Mixed upper and lower motor neuron disease. Loss of ambulation typically occurs 15 years after disease onset. More than 95% of patients are wheelchair bound by age 45 years.

Estimated 1:30,000-50,000 in the general population. Carrier frequency is 1:60-110 with a disease prevalence of 1:29,000. Incidence is low in Africans and Asians.

Autosomal recessive. Gene map locus is 9q13. FRDA is associated with a mutation that consists of unstable expansion of GAA repeats on chromosome 9. FRDA alleles are found in approximately 11.4% of apparently recessive patients and 5.2% of apparently sporadic patients.

Spinocerebellar degeneration involving the spinocerebellar tracts, dorsal columns, pyramidal tracts, and, to a lesser extent, the cerebellum and medulla. Frataxin, the protein produced by the FRDA gene, which is part of the cellular energy of mitochondria, is severely reduced in the nervous system, heart, and pancreas of patients with FRDA. Patients have abnormally high levels of iron in their heart tissue and it is believed that the nervous system, heart, and pancreas may be particularly susceptible to damage from the free radicals produced when the excess iron reacts with oxygen. Many enzymatic activities are defective, but reduced activity of FE-S cluster-containing subunits (located in mitochondrial complexes I, II, and III and in aconitase) play a major role in disease progression.

Neurologic examination, EMG, muscle biopsies, and measurement of nerve conduction. Direct molecular test of GAA expansion is useful for the diagnosis, prognosis (size of GAA expansion is associated with the frequency of cardiomyopathy and loss of reflexes in the upper limbs), and genetic counseling. Prenatal diagnosis is available.

Symptoms usually begin between the ages of 5 and 15 years but can appear earlier. The first sign is usually difficulty in walking. The ataxia gradually worsens and slowly spreads to the arms and trunk. Foot deformities, such as clubfoot, flexion of the toes, hammertoes, or foot inversion, may be early signs. Rapid, rhythmic, involuntary movements of the eyeball are common. Most people with FRDA develop scoliosis, which may be extremely severe. Hypertrophic cardiomyopathy and congestive heart failure (often a cause of death) are usual. Of patients with FRDA, 25% have diabetes mellitus; diabetic ketosis is not infrequent.

For elective surgery, an anesthesiology consultation is highly recommended. Evaluate neurologic status (preferably with the help of an ...

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