Spinocerebellar ataxia type 3 phenotypically resembling Parkinson disease in a black family

Background: Machado-Joseph disease (MJD),also known as spinocerebellar atax ia type 3 (SCA3), can present with parkinsonism. However, classically, atyp ical features, including pyramidal and cerebellar signs, peripheral neuropa thy, and/or anterior horn cell dysfunction, are also seen. Levodopa respons iveness is unusual in this disorder. Objective: To determine the cause of apparent parkinsonism suggestive of Pa rkinson disease (PD) in a large family of African origin. Methods: We studied a large family in which apparent autosomal dominant par kinsonism suggestive of PD occurs in order to find the causal genetic mutat ion. Affected and unaffected family members were screened for the presence of a pathogenic expansion at the MJD/SCA3 locus using a polymerase chain re action polyacrylamide gel electrophoresis-based assay. Results: Three of the 4 individuals who were examined have a phenotype remi niscent of PD. Specifically, they have at least 2 of the cardinal features, are levodopa responsive, and have no atypical features. All affected famil y members were shown to possess pathogenic expansions in the MJD/SCA3 gene. Conclusions: Parkinsonism suggestive of PD due to MJD/SCA3 has not been pre viously 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 A frican ancestry. In this regard, it is perhaps significant that all the ind ividuals with parkinsonism have relatively low numbers of repeats (normal, 16-34; pathologic, 60-84). In families in which linkage analysis is being p erformed to determine a locus for autosomal dominant parkinsonism suggestiv e of PD, evaluation for the MJD/SCA3 mutation is indicated.