Friedreich’s ataxia - Hereditary and congenital disorders

Friedreich’s ataxia

Definition

Progressive degenerative spastic cerebellar ataxia occurring in the young.

Incidence

Rare, but it is the most common hereditary ataxia.

Age

Difficulty in walking occurs around age 12.

Aetiology/pathophysiology

It is an autosomal recessive condition. In most cases there is an abnormal expanded sequence of trinucleotide (GAA) repeats in the gene for frataxin. These repeats result in lower expression of the gene product, a mitochondrial protein. The number of repeats tends to elongate in subsequent generations which results in a worse clinical picture (genetic anticipation). Frataxin appears to protect against oxidative damage particularly in the brain, heart and pancreas. The neuropathological change is of degeneration of the posterior columns, corticospinal and spinocerebellar tracts.

Clinical features

·        Progressive ataxia of all four limbs and trunk. Pyramidal weakness and extensor plantars.

·        Absent joint position and vibration sense in the lower limbs.

·        Absent reflexes in the lower limbs. Pes cavus.

·        Cerebellar dysarthria. Nystagmus in 25%.

·        Optic atrophy in 30%.

·        Cardiomyopathy with T-wave inversion, left ventricular hypertrophy, arrhythmias.

·        Diabetes mellitus occurs in about a third.

Investigations

Genetic testing and counselling.

Management

Cardiac arrhythmias should be controlled and ACE inhibitors may improve left ventricular hypertrophy. Diabetes may require dietary change, oral hypoglycaemics or insulin. Physiotherapy and orthopaedic intervention for skeletal deformity may be of benefit.

Prognosis

Death is usual before the age of 40, mainly due to complications of diabetes and heart disease.