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