Abstract

The m.8993T→C MTATP6 mutation of mitochondrial DNA (mtDNA) usually causes mitochondrial disease in childhood, but was recently described in a family with adult onset ataxia and polyneuropathy. Cytochrome c oxidase muscle histochemistry, which is the standard clinical investigation for mitochondrial disease in adults, is usually normal in patients with MTATP6 mutations. This raises the possibility that these cases have been missed in the past. We therefore studied 308 patients with unexplained ataxia and 96 patients with suspected Charcot–Marie–Tooth disease to determine whether the m.8993T→C MTATP6 mutation is common in unexplained inherited ataxia and/or polyneuropathy. We identified a three-generation family with the m.8993T→C mutation of mtDNA. One subject had episodic ataxia (EA) and transient hemipareses, broadening the phenotype. However, no further cases were identified in an additional cohort of 191 patients with suspected EA. In conclusion, m.8993T→C MTATP6 should be considered in patients with unexplained ataxia, CMT or EA, but cases are uncommon.