Background Spinocerebellar ataxia syndromes presenting in adulthood have a broad range of causes, and despite extensive investigation remain undiagnosed in up to ∼50% cases. Mutations in the mitochondrially encoded MTATP6 gene typically cause infantile-onset Leigh syndrome and, occasionally, have onset later in childhood. The authors report two families with onset of ataxia in adulthood (with pyramidal dysfunction and/or peripheral neuropathy variably present), who are clinically indistinguishable from other spinocerebellar ataxia patients.
Methods Genetic screening study of the MTATP6 gene in 64 pedigrees with unexplained ataxia, and case series of two families who had MTATP6 mutations.
Results Three pedigrees had mutations in MTATP6, two of which have not been reported previously and are detailed in this report. These families had the m.9185T>C and m.9035T>C mutations, respectively, which have not previously been associated with adult-onset cerebellar syndromes. Other investigations including muscle biopsy and respiratory chain enzyme activity were non-specific or normal.
Conclusions MTATP6 sequencing should be considered in the workup of undiagnosed ataxia, even if other investigations do not suggest a mitochondrial DNA disorder.
- spinocerebellar ataxia
- clinical neurology
- mitochondrial disorders
- muscular dystrophy
- muscle disease
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Funding Funding for this work originated from the Wellcome Trust, Research Council (UK), the UK NIHR Biomedical Research Centre for Ageing and Age-related disease award to the Newcastle-upon-Tyne Foundation Hospitals NHS Trust and the UK NHS Specialised Services which supports the Rare Mitochondrial Disorders of Adults and Children Diagnostic Service (http://www.mitochondrialncg.nhs.uk) in Newcastle-upon-Tyne. GP receives funding from the Clinician Investigator Program from the University of British Columbia (Vancouver, Canada), and a Bisby Fellowship from the Canadian Institutes of Health Research. PFC is a Wellcome Trust Senior Clinical Fellow and NIHR Senior Investigator.
Competing interests None.
Patient consent Patients provided written informed consent for participation in this research. Our data are presented anonymously without any identifiers and, therefore, we did not obtain additional consent for submission of this work to Journal of Neurology, Neurosurgery and Psychiatry.
Ethics approval Ethics approval was granted by the Newcastle University Clinical Research Ethics Board.
Provenance and peer review Not commissioned; externally peer reviewed.