LAUSR

MT-ATP6-associated disease is caused by mutations in the mitochondrial gene MT-ATP6, encoding a subunit of the ATP synthase complex. Clinically, MT-ATP6 mutations were first associated with a syndrome combining neuropathy, ataxia, and retinitis pigmentosa (NARP syndrome) as well as with Leigh syndrome in more than 50% of patients. However, it has recently been shown that the phenotypic spectrum of MT-ATP6-associated disease is much broader, ranging from asymptomatic subjects via rather mild adult-onset CMT-like phenotypes to earlyonset multisystemic neurodegeneration. An 18-year-old female presented with a progressive complex ataxic gait disorder since early childhood. She had learned to walk only at age 3 years with frequent falls persisting and increasing inward rotation of the feet. She lost the ability to walk freely at age 6 years, with full wheelchair-dependency from age 10 years. Neurological examination showed severe distal muscular atrophies, mild tetraparesis, bidirectional gazeevoked and upbeat nystagmus in primary position. Distal loss of vibration sensation and absent deep tendon reflexes were noted. Ataxia was apparent by ataxic-paretic gait, dysmetric heel-shin slide and truncal ataxia, with a Scale for the Assessment and Rating of Ataxia (SARA) score of 17 points at initial examination, worsening to 18.5 points at 1-year-follow-up. Nerve conduction studies showed axonal sensorimotor polyneuropathy. Motorevoked potentials indicated pyramidal tract lesions. Targeted NGS revealed a known pathogenic homoplasmic MT-ATP6 mutation (m.8993T > C; p.L156P) that has been associated with a Leigh syndrome clinically and on MRI. Sequential neuroimaging at age 15 revealed development of T2-hyperintensities (Fig A,B) and corresponding T1-hypointense signal (Fig C,D) at the bottom of cerebellar fissures compared to initial MRI 10 years earlier at age 5 years (Fig E,F). Ethical approval was granted by the local ethics committee (#598/2011BO1) and written informed consent from the patient and her legal guardian were obtained prior to study inclusion. MRI signal alterations are frequent findings in mitochondrial disorders, e.g. necrotic, T2-hyperintense lesions of the basal ganglia in Leigh syndrome. In MT-ATP6-