Article

Ataxia with ocular motor apraxia type 1 (AOA1) is an autosomal recessive
cerebellar ataxia (ARCA) associated with oculomotor apraxia, hypoalbuminaemia and
hypercholesterolaemia. The gene APTX, which encodes aprataxin, has been
identified recently. We studied a large series of 158 families with
non-Friedreich progressive ARCA. We identified 14 patients (nine families) with
five different missense or truncating mutations in the aprataxin gene (W279X,
A198V, D267G, W279R, IVS5+1), four of which were new. We determined the relative
frequency of AOA1 which is 5%. Mutation carriers underwent detailed neurological,
neuropsychological, electrophysiological, oculographic and biological
examinations, as well as brain imaging. The mean age at onset was 6.8 +/- 4.8
years (range 2-18 years). Cerebellar ataxia with cerebellar atrophy on MRI and
severe axonal sensorimotor neuropathy were present in all patients. In contrast,
oculomotor apraxia (86%), hypoalbuminaemia (83%) and hypercholesterolaemia (75%)
were variable. Choreic movements were frequent at onset (79%), but disappeared in
the course of the disease in most cases. However, a remarkably severe and
persistent choreic phenotype was associated with one of the mutations (A198V).
Cognitive impairment was always present. Ocular saccade initiation was normal,
but their duration was increased by the succession of multiple hypometric
saccades that could clinically be confused with 'slow saccades'. We emphasize the
phenotypic variability over the course of the disease. Cerebellar ataxia and/or
chorea predominate at onset, but later on they are often partially masked by
severe neuropathy, which is the most typical symptom in young adults. The
presence of chorea, sensorimotor neuropathy, oculomotor anomalies, biological
abnormalities, cerebellar atrophy on MRI and absence of the Babinski sign can
help to distinguish AOA1 from Friedreich's ataxia on a clinical basis. The
frequency of chorea at onset suggests that this diagnosis should also be
considered in children with chorea who do not carry the IT15 mutation responsible
for Huntington's disease.

Langue : ANGLAIS