Adult-onset spinocerebellar ataxia syndromes due to MTATP6 mutations.

Abstract

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.

• Authors: Gerald Pfeffer, Emma L Blakely, Charlotte L Alston, Adam Hassani, Mike Boggild, Rita Horvath, David C Samuels, Robert W Taylor, Patrick F Chinnery
• Journal: Journal of neurology, neurosurgery, and psychiatry (J Neurol Neurosurg Psychiatry) Vol. 83 Issue 9 Pg. 883-6 (Sep 2012) ISSN: 1468-330X [Electronic] England
• PMID: 22577227 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MT-ATP6 protein, human
• Mitochondrial Proton-Translocating ATPases

Topics

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