Cerebellar Ataxia and CoQ10 Deficiency.

In 2001, we described six patients with cerebellar ataxia and severe deficiency of coenzyme Q10 (CoQ10, ubiquinone) in skeletal muscle [1]. Within one year, we described 13 additional patients [2]; therefore, we suspected this was not a very rare syndrome. Twelve years after our original report, cerebellar ataxia and atrophy has emerged as the most common clinical presentation of CoQ10 deficiency, and now we know that it can be primary (associated with mutations in genes coding proteins involved in the biosynthesis of CoQ10 or its regulation), or secondary to other causes. In fact, 3 of the first patients reported by Musumeci et al. have a homozygous mutation in APTX, encoding aprataxin [3], a protein involved in DNA break repair, and one of the patients reported by Lamperti et al. carried heterozygous mutations in ADCK3/CABC1, which encodes a kinase required for CoQ10 biosynthesis [4]. To date, mutations in ADCK3/CABC1 have been identified in 21 patients (14 families), some of them presenting with cerebellar ataxia and atrophy, plus exercise intolerance, dystonia and mild cognitive impairment [49]. Secondary CoQ10 deficiency has been confirmed in additional patients carrying APTX mutations [3,10-12].