spinocerebellar ataxia type 3 (SCA-3); Machado-Joseph disease; Azorean disease

Introduction

see NINDS Machado-Joseph Disease Information Page

Epidemiology

• most common autosomal dominant spinocerebellar ataxia

Genetics

• autosomal dominant
• increased number of CAG repeats in SCA3 gene 40 - 200 vs 12-41 in wild-type allele
• wild-type SCA3 protein is cytoplasmic in neurons vs nuclear for mutant allele
• AGAP3 also translocates from cytoplasm to PML nuclear bodies

Clinical manifestations

• ataxia
• slow saccades & saccadic pursuit
• sign of brainstem dysfunction may be present
  • dysarthria, dyphagia, poor cough, tongue fasciculations
• signs of upper & lower motor neuropathy
  • hyptonia to rigidity
  • exagerated to absent reflexes
  • Babinsky sign
• extrapyramidal signs: rigidity, dystonia
• cognitive impairment, verbal & visual memory impairment, impairment of verbal fluency, visuospatial impairment, constructional dysfunction
• autonomic dysfunction
  • cold intolerance, nocturia, orthostatic dizziness

More general terms

• spinocerebellar ataxia (SCA)
• polyglutamine expansion disorder

Patient information

spinocerebellar ataxia type 3; Machado-Joseph disease patient information

Database

• OMIM: https://mirror.omim.org/entry/109150
• OMIM: https://mirror.omim.org/entry/607047
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4287