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Spinocerebellar Ataxia Type 3 Phenotypically Resembling Parkinson Disease in a Black Family
Katrina Gwinn-Hardy, MD;
Andrew Singleton, PhD;
Padraig O'Suilleabhain, MD;
Michael Boss, PhD;
David Nicholl, MD;
Amanda Adam, BS;
Jennifer Hussey, BA;
P. Critchley, MD;
John Hardy, PhD;
Matthew Farrer, PhD
Arch Neurol. 2001;58:296-299.
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.
From the Department of Pharmacology, Mayo Clinic Jacksonville, Jacksonville,
Fla (Drs Gwinn-Hardy, Singleton, Hardy, and Farrer and Mss Adam and Hussey);
the Departments of Neurology, University of Texas Southwestern Medical Center
at Dallas (Dr O'Suilleabhain), Queen Elizabeth Hospital, Birmingham, England
(Dr Nicholl), and the Leicester Royal Infirmary, Leicester, England (Dr Critchley);
and Athena Diagnostics Corporation, Worcester, Mass (Dr Boss).
Corresponding author and reprints: Katrina Gwinn-Hardy, MD, Mayo
Clinic Jacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224 (e-mail: gwinn.katrina{at}mayo.edu).
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