Spinocerebellar Ataxia Type 3

a.k.a. Machado-Joseph Disease

SCA3 or Machado-Joseph disease is the most common recognized form of SCA in most populations. The proportion of SCA patients with SCA3 ranges from 7% in India (0% in South Africa and Italy) to 74% in Portugal, and is found in about 21% of US SCA patients. The age of onset of SCA3 usually the 2nd to the 4th decade. There are also reports of rare childhood-onset variants with severe disease, as well as variants with rigidity. Initial symptoms are usually unsteadiness or stiffness of gait, clumsiness, and slurred speech, but a significant proportion of patients develop diplopia before any gait difficulty. Typically the disease is slowly progressive, leading to the need for assistive devices including a wheelchair 10 to 15 years after onset. Death results from pulmonary complications and cachexia from 6 to 29 years after onset. SCA3/Machado Joseph disease (MJD) is due to an expansion of a CAG repeat expansion in the SCA3/MJD gene on 14q32.1 that leads to an elongated tract of glutamine residues within a novel, nucleocytoplasmic protein, ataxin-3. The diagnosis of SCA3 is established by the demonstration of an expansion in one CAG repeat alleles in the SCA3 locus greater than 55 repeats in an ataxia patient.