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spinocerebellar ataxia type 3 (SCA-3); Machado-Joseph disease; Azorean disease
see NINDS Machado-Joseph Disease Information Page
Epidemiology:
- most common autosomal dominant spinocerebellar ataxia
Genetics:
1) autosomal dominant
2) increased number of CAG repeats in SCA3 gene 40 - 200 vs 12-41 in wild-type allele
3) wild-type SCA3 protein is cytoplasmic in neurons vs nuclear for mutant allele
4) AGAP3 also translocates from cytoplasm to PML nuclear bodies
Clinical manifestations:
1) ataxia
2) slow saccades & saccadic pursuit
3) sign of brainstem dysfunction may be present
- dysarthria, dyphagia, poor cough, tongue fasciculations
4) signs of upper & lower motor neuropathy
a) hyptonia to rigidity
b) exagerated to absent reflexes
c) Babinsky sign
5) extrapyramidal signs: rigidity, dystonia
6) cognitive impairment, verbal & visual memory impairment, impairment of verbal fluency, visuospatial impairment, constructional dysfunction
7) autonomic dysfunction
- cold intolerance, nocturia, orthostatic dizziness
General
polyglutamine expansion disorder
spinocerebellar ataxia (SCA)
Database Correlations
OMIM correlations
Entrez Gene 4287
References
- Duenas AM et al,
Molecular pathogenesis of spinocerebellar ataxias.
Brain. 2006, 120:1357
PMID: 16613893
- Koeppen AH et al,
The pathogenesis of spinocerebellar ataxia.
Cerebellum 2005, 4:62
PMID: 15895563
- Sudarsky L and Coutino P
Machado-Joseph disease.
Clin Neurosci 1995, 3:17
PMID: 7614089
- UpToDate version 14.2
- OMIM :accession 109150
- NINDS Machado-Joseph Disease Information Page
https://www.ninds.nih.gov/disorders/all-disorders/machado-joseph-disease-information-page