title: Caring for Machado-Joseph disease: current understanding and how to help patients.
abstract: Machado-Joseph disease or spinocerebellar ataxia 3 (MJD/SCA3) is a clinically heterogeneous, neurodegenerative disorder characterized by varying degrees of ataxia, ophthalmoplegia, peripheral neuropathy, pyramidal dysfunction and movement disorder. MJD/SCA3 is caused by a CAG repeat expansion mutation in the protein coding region of the ATXN3 gene located at chromosome 14q32.1. Current hypotheses regarding pathogenesis favor the view that mutated ataxin-3, with its polyglutamine expansion, is prone to adopt an abnormal conformation, engage in altered protein-protein interactions and aggregate. Expanded CAG repeat length correlates with the range and severity of the clinical manifestations and inversely correlates with age of disease onset. Though MJD/SCA3 is classically described as affecting the cerebellum, brainstem and basal ganglia, recent neuropathology and neuroimaging series demonstrate involvement of other areas such as the thalamus and cerebral cortex. Clinically, much emphasis has been placed in the description and recognition of the non-motor symptoms observed in these patients, such as pain, cramps, fatigue and depression. Currently, no disease modifying treatment exists for MJD/SCA3. Standard of care includes genetic counseling, exercise/physical therapy programs, and speech and swallow evaluation. Symptomatic treatment for clinical findings such as depression, sleep disorders, parkinsonism, dystonia, cramps, and pain is important to improve the quality of life for those with MJD/SCA3.
authors.affiliation: Department of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Anelyssa
authors.initials: A
authors.lastname: D'Abreu
authors.forename: Marcondes C
authors.initials: MC
authors.lastname: França
authors.forename: Henry L
authors.initials: HL
authors.lastname: Paulson
authors.forename: Iscia
authors.initials: I
authors.lastname: Lopes-Cendes
mesh_terms: D000067699:Ataxin-3; D003952:Diagnostic Imaging; D005838:Genotype; D006801:Humans; D017827:Machado-Joseph Disease / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3