Background: Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), can present with parkinsonism. However, classically, atypical features, including pyramidal and cerebellar signs, peripheral neuropathy, and/or anterior horn cell dysfunction, are also seen. Levodopa responsiveness is unusual in this disorder.
Objective: To determine the cause of apparent parkinsonism suggestive of Parkinson disease (PD) in a large family of African origin.
Methods: We studied a large family in which apparent autosomal dominant parkinsonism suggestive of PD occurs in order to find the causal genetic mutation. Affected and unaffected family members were screened for the presence of a pathogenic expansion at the MJD/SCA3 locus using a polymerase chain reaction polyacrylamide gel electrophoresis-based assay.
Results: Three of the 4 individuals who were examined have a phenotype reminiscent of PD. Specifically, they have at least 2 of the cardinal features, are levodopa responsive, and have no atypical features. All affected family members were shown to possess pathogenic expansions in the MJD/SCA3 gene.
Conclusions: Parkinsonism suggestive of PD due to MJD/SCA3 has not been previously reported, to our knowledge. However, atypical, though also levodopa-responsive, parkinsonism has been previously reported to occur in African American families, suggesting that that this phenotype is associated with African ancestry. In this regard, it is perhaps significant that all the individuals with parkinsonism have relatively low numbers of repeats (normal, 16-34; pathologic, 60-84). In families in which linkage analysis is being performed to determine a locus for autosomal dominant parkinsonism suggestive of PD, evaluation for the MJD/SCA3 mutation is indicated.