Ataxia with oculomotor apraxia 1 (AOA1) in a consanguineous Pakistanian familiy

Aims: Ataxia with oculomotor apraxia 1 (AOA1) is a rare autosomal-recessive inherited ataxia caused by mutations in the APTX gene. Manifestation since early childhood has been reported. A causal therapy is not available; in some patients with reduced coenzyme Q10 measurement in muscle specimen positive effects of coenzyme Q10 substitution have been described.

Patients und methods: We report on a consanguineous family from Pakistan with three affected children (13-year-old female patient and her two 11-year-old twin-sisters) and their 35-year-old uncle with AOA1. All affected family members showed a delayed motor development in the first years of life, and additionally, cerebellar symptoms since the age of three years. During clinical follow-up symptoms of ataxia, dysarthria and peripheral axonal neuropathy increased. Cranial magnet resonance imaging of the girls disclosed cerebellar atrophy, especially vermis atrophy. Loss of ambulation in the uncle at the age of 9 years was reported; currently, he suffers from a severe peripheral axonal neuropathy causing muscular atrophy and from oculomotor apraxia. Genetic analysis in our family disclosed homozygosity for the mutation c.430C>T, Exon 4 in the APTX gene in the 13-year-old girl and her uncle; further genetic analysis in our family is in progress. Coenzyme Q10 measurements in muscle specimen of the uncle showed normal results; therefore, no substitution of coenzyme Q10 has been started so far.

Conclusions: Clinical symptoms of AOA1 will be demonstrated by video presentation of two affected family members. Substitution of coenzyme Q10 as a therapeutic option in this disease will be discussed.