ABSTRACT
In the 1970s, the disease known as Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (SCA3/MJD) was first described in American families who descended from immigrants out of the Portuguese Islands of the Azores. It is a fitting testimony to SCA3/MJD’s wide-ranging clinical heterogeneity that the disease was independently reported in three separate families as distinct syndromes. In addition to relatively mild ataxia, type 3 patients develop prominent peripheral neurological signs, including muscle cramping, motor neuron loss, distal wasting and sensory neuropathy. Less than a third of SCA3/MJD patients have type 1 or 3 disease. The neuropathy is usually symmetric, involving sensory and motor neurons and both unmyelinated and myelinated fibres. The neuropathy of SCA3/MJD may represent axonal degeneration secondary to neuronal damage centrally, although this has not been proven. A systematic search for ubiquitin abnormalities in neuronal processes may help determine whether protein aggregation in the cytoplasm contributes to the axonal neuropathy of SCA3/MJD.
