Machado-Joseph disease (MJD) also known as Spinocerebellar ataxia type 3, is a hereditary neurodegenerative disease associated with severe clinical manifestations and premature death. Although rare, it is the most common autosomal dominant spinocerebellar ataxia worldwide and has a distinct geographic distribution, reaching peak prevalence in certain regions of Brazil, Portugal and China. Due to its clinical heterogeneity, it was initially described as several different entities and as had many designations over the last decades. An accurate diagnosis become possible in 1994, after the identification of the MJD1 gene. Among its wide clinical spectrum, progressive cerebellar ataxia is normally present. Other symptoms include pyramidal syndrome, peripheral neuropathy, oculomotor abnormalities, extrapyramidal signs and sleep disorders. On the basis of the presence/absence of important extra-pyramidal signs, and the presence/absence of peripheral signs, five clinical types have been defined. Neuroimaging studies like MRI, DTI and MRS, can be useful as they can characterize structural and functional differences in specific subgroups of patients with MJD. There is no effective treatment for MJD. Symptomatic therapies are used to relieve some of the clinical symptoms and physiotherapy is also helpful in improving quality of live. Several clinical trials have been carried out using different molecules like sulfamethoxazole-trimethoprim, varenicline and lithium carbonate, but the results of these trials were negative or showed little benefit. Future studies sufficiently powered and adequately designed are warranted.
Keywords: Machado-Joseph disease; Natural history; Pharmacological treatment; Polyglutamine diseases; Spinocerebellar ataxia type 3.