Two cases of ataxia with oculomotor apraxia type 1 (AOA1) without muscle coenzyme Q10 deficiency

Background: Mutations in the aprataxin gene (APTX) cause early onset ataxia with oculomotor apraxia type 1 (AOA1), an autosomal recessive disorder associated with cerebellar atrophy, axonal sensorimotor neuropathy, hypoalbuminaemia and hypercholesterolaemia. It has been shown recently that aprataxin gene mutations are also associated with muscle coenzyme Q10 (CoQ10) deficiency and that patients with aprataxin mutations and muscle coenzyme Q10 deficiency improved clinically after coenzyme Q10 supplementation. Recent studies suggested a correlation of the nature of the mutation and the levels of muscle coenzyme Q10.

Objective: Our aim was to determine muscle CoQ10 levels as a potential target of treatment in patients with AOA1.

Patients and methods: Two female patients with genetically proven AOA1 were clinically examined and underwent open muscle biopsy of vastus lateralis muscle. We performed morphological studies and analysis of respiratory chain complexes, muscle CoQ10 levels were measured in total and referred to the activity of citrate synthase.

Main results: Both patients showed normal CoQ10 levels in muscles. One patient carried a homozygous W279X mutation, one was compound heterozygous for the E240X/T221X mutations.

Conclusion: Not all patients with AOA1 show muscle CoQ10 deficiency. Our results do not confirm low levels of muscle CoQ10 in homozygous W279X mutation carriers. Therefore determination of muscle CoQ10 in AOA1 patients is necessary to asses benefit from oral CoQ10 supplementation. Further studies are needed to determine closer the genotype-phenotype correlation of AOA1 and muscle CoQ10 deficiency and to learn more about the interaction of mutated aprataxin and CoQ10 metabolism.