Mitochondrial G8363A mutation presenting as cerebellar ataxia and lipomas in an Italian family

Abstract

We report an Italian family harboring the mitochondrial DNA (mtDNA) G8363A mutation in the tRNALys gene in association with various combinations of encephalopathy, ophthalmoparesis, and horse collar lipomas. These findings add to the complex relationship between mtDNA pathogenetic mutations and disease phenotype. The proband (III-10), a 22-year-old man, developed normally until age 9 years, when he had progressive gait ataxia and dysarthria. Neurologic examination also showed progressive external ophthalmoparesis, dysphagia, myoclonic jerks, and bilateral hearing impairment. Venous lactic acid was elevated (5 mmol/L; normal <2.4 mmol/L). The maternal grandmother (I-1) reportedly had a late-onset gait disorder. Our proband’s mother (II-4) started to have gait and truncal ataxia at age 22. At age 60, neurologic examination revealed limited upper gaze, mild hearing impairment, and brisk tendon reflexes. Her serum lactate was 2.7 mmol/L. Similar clinical features were found in Patients II-5 and II-6, whose onset was in late adolescence. In addition, Patients II-4, II-5, and II-6 …