Spinocerebellar Ataxia 3 (SCA3); Machado-Joseph Disease
Inheritance
Autosomal dominant, with anticipation unrelated to sex of the transmitting parent.
Molecular genetics and pathogenesis
SCA 3 is due to an expanded CAG repeat in a coding region of the SCA3 gene, encoding ataxin-3, a protein thought to be involved in processing of other proteins. Ataxin-3 is also called MJD protein 1. Like the other dominant polyglutamine diseases, the toxic effect is believed to be primarily due to a gain of function of the mutated protein, rather than a lost function of the wild-type.
Clinical manifestations
Ataxia of limbs, gait, speech, eye movements; double vision; bulging eyes; difficulty speaking and swallowing; exaggerated reflexes; extrapyramidal signs, especially parkinsonism and dystonia; mild cognitive impairment; peripheral neuropathy.
Treatment
Several randomized trials have been performed in SCA 3, but no drug has proved effective.
References
Paulson HL. Dominantly inherited ataxias: lessons learned from Machado-Joseph disease/spinocerebellar ataxia type 3. Semin Neurol. 2007 Apr;27(2):133-42.
PMID: 17390258
OMIM
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109150
