INSTRUCTION

Perform a neurological examination of this patient's legs.

SALIENT FEATURES

History

· Age of onset (usually the same in each family and ranges from 8 to 16 years of age).

· High-arched foot in childhood in the family (Friedreich's foot).

· Scoliosis developing in childhood.

· Cerebellar dysarthria and ataxia

Examination

· Pes cavus.

· Pyramidal weakness in legs.

· Cerebellar signs, ataxia being a constant sign.

· Impaired vibration and joint sense.

· Romberg's sign positive.

· Absence of deep tendon reflexes (due to degeneration of peripheral nerves)

· Distal muscle wasting (in 50% of cases), especially in the hands.

Proceed as follows:

· Check for nystagmus (present in 25% of the cases), scanning speech, intention tremor.

· Examine the heart for hypertrophic cardiomyopathy.

· Check the eyes for optic atrophy (present in 30% of cases).

· Check the spine for kyphoscoliosis.

· Check the urine for sugar (10% of patients have diabetes).

· Check IQ, looking for intellectual deterioration.

DIAGNOSIS

This patient has kyphoscoliosis, pes cavus and a combination of pyramidal, cerebellar and sensory deficits (lesions) in the lower

limbs due to Friedreich's ataxia (aetiology); he is severely disabled by his deformity.

ADVANCED-LEVEL QUESTIONS

What is the mode of inheritance?

Autosomal recessive or, rarely, sex linked.

Why are the deep tendon reflexes absent even though plantars are upgoing?

This is due to a combination of pyramidal weakness with peripheral neuropathy.

In which other condition is there a mixture of cerebellar, pyramidal and dorsal column signs?

Multiple sclerosis.

Mention a few conditions with absent knee jerks and upgoing plantars.

· Peripheral neuropathy in a stroke patient.

· Motor neuron disease.

· Conus medullaris - cauda equina lesion.

· Tabes dorsalis.

· Subacute combined degeneration of the spinal cord.

What is the forme fruste of this condition?

Pcs cavus or hammer toes, without any other signs, are seen in family members of such patients.

On which chromosome is the gene for this disorder localized? Chromosome 9.

What are the clinical criteria for diagnosis of Friedreich's ataxia? Harding's criteria (Brain 1981; 104: 589):

· Essential criteria are onset before the age of 25 years, ataxia of limbs and gait, absent knee and ankle jerks, extensor plantars,

autosomal recessive inheritance, motor conduction velocity greater than 40 ms, small or absent sensory nerve action

potentials, dysarthria within 5 years of onset.

· Additional criteria (present in two thirds) are scoliosis, pyramidal weakness of lower limbs, absent upper limb reflexes, loss of

vibration and joint position sense in the legs, abnormal ECG, pcs cavus.

· Other features (present in less than 50% of cases) are nystagmus, optic atrophy, deafness, distal muscle wasting and diabetes.

What is the prognosis of Friedreich's ataxia ?

Friedreich's ataxia usually progresses slowly and few patients live for more than 20 years after the onset of symptoms. Occasionally

it may appear to be arrested, and abortive cases may be encountered in apparently healthy relatives of affected patients.

What are the pathological changes in Friedreich's ataxia?

· Marked loss of cells in the posterior root ganglia.

· Degeneration of peripheral sensory fibres.

· Involvement of the posterior and lateral columns of the cord.

Name a few syndromes with spinocerebellar degeneration (N Engl J Med 1995; 333: 1351-3).

· Roussy-Ldvy disease: hereditary spinocerebellar degeneration with atrophy of lower limb muscles and loss of deep tendon

reflexes.

· Refsum's disease (see p. 537).

· Bassen-Kornzweig syndrome (see p. 537): caused by cellular deficiency of vitamin E (alpha-tocopherol) resulting from a defect

in the alpha-tocopherol-transfer protein and abetalipoproteinaemia associated with a defect of very low density lipoproteins.

· Olivopontocerebellar degeneration: first described in 1882; autosomal dominant inheritance and has been mapped to HLA loci

on the short arm of chromosome 6;

a highly polymorphic CAG repeat sequence has been found in this region. The CAG repeat sequence is longer than normal and unstable in affected

patients.

· Machado Joseph disease: dominant inheritance, first described in families of Portuguese origin. Clinical features include progressive ataxia,

ophthalmoparesis, spasticity, dystonia, amyotrophy and parkinsonism. This disorder has been linked to chromosome 14 and is caused by the

expansion of unstable CAG repeat sequences.

· Dentatorubral pallidoluysian atrophy is similar to Machado-Joseph disease but maps on the short arm of chromosome 12. The abnormally

expanded CAG repeat sequences identified in the gene for olivopontocerebellar degeneration, Machado-Joseph disease and dentatorubral

pallidoluysian atrophy each result in the expression of a specific ataxin.

Nikolaus Friedreich (1825-1882), Professor of Pathology and neurologist in Heidelberg, described this condition in a series of papers from 1861 to

1876.

Anita Harding (1953-1995) Professor of Neurology at the National Hospital, Queen Square, London, died at the age of 42 years from colonic cancer.

G. Roussy (1874-1948), a French neuropathologist.

G. Levy (b. 1881), a French neurologist.

Sigvald Refsum (1907-1991), a Norwegian neurologist, was successively Professor of Neurology at Bergen University and at the National Hospital in

Oslo (BMJ 1991; 303: 919).