Chinese patients with Machado-Joseph disease presenting with complicated hereditary spastic paraplegia

Background and purpose:  The clinical overlap between Machado-Joseph disease (MJD) and autosomal dominant complicated hereditary spastic paraplegia (AD-HSP) is extensive and the differentiation between them can be difficult on clinical ground. However, patients are seeking the right diagnosis and it is important for neurologists to distinguish them in the early stage.
Methods:  In recent 10 years, we have recruited and followed-up three families which were initially diagnosed as complicated AD-HSP based on the clinical criteria. Mutation analyses of SPG4 , SPG3A and ATXN3 were performed in the index cases.
Results:  No mutations on SPG4 and SPG3A were found. Mutation analysis of ATXN3 showed that these cases have one expanded allele and one normal allele. The copy numbers of CAG repeats were 80/28, 86/28 and 83/33, respectively.
Conclusions:  The molecular diagnosis confirmed that they were MJD patients though they had been misdiagnosed as complicated AD-HSP for many years. The copy numbers of expanded allele were more than 80 and the copy numbers of normal allele were more than 27, which could somewhat explain the earlier onset age of these cases and the anticipation of the pedigrees. Our data emphasize the necessity to perform the mutation analysis of ATXN3 in clinically diagnosed complicated AD-HSP patients.