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.