Adult-onset spinocerebellar ataxia syndromes due to MTATP6 mutations.

Pfeffer G, Blakely EL, Alston CL, Hassani A, Boggild M, Horvath R, Samuels DC, Taylor RW, Chinnery PF
J Neurol Neurosurg Psychiatry. 2012 83 (9): 883-6

PMID: 22577227 · PMCID: PMC4034166 · DOI:10.1136/jnnp-2012-302568

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.

MeSH Terms (12)

Adult Age of Onset Child, Preschool Female Genetic Testing Humans Male Middle Aged Mitochondrial Proton-Translocating ATPases Mutation Pedigree Spinocerebellar Ataxias

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