Machado–Joseph disease

Machado–Joseph disease (MJD), also known as Machado–Joseph Azorean disease, Machado's disease, Joseph's disease or spinocerebellar ataxia type 3 (SCA3), is a rare autosomal dominantly inherited neurodegenerative disease that causes progressive cerebellar ataxia, which results in a lack of muscle control and coordination of the upper and lower extremities. The symptoms are caused by a genetic mutation that results in an expansion of abnormal 'CAG' trinucleotide repeats in the ATXN3 gene that results in an abnormal form of the protein ataxin which causes degeneration of cells in the hindbrain. Some symptoms, such as clumsiness and rigidity, make MJD commonly mistaken for drunkenness or Parkinson's disease. Machado–Joseph disease is a type of spinocerebellar ataxia and is the most common cause of autosomal-dominant ataxia. MJD causes ophthalmoplegia and mixed sensory and cerebellar ataxia. Symptoms of MJD are memory deficits, spasticity, difficulty with speech and swallowing, weakness in arms and legs, clumsiness, frequent urination and involuntary eye movements. Symptoms can begin in early adolescence and they get worse over time. Eventually, MJD leads to paralysis; however, intellectual functions usually remain the same. Flores and São Miguel are centers of the Machado–Joseph disease in the Azores. Machado Joseph's disease has multiple origins as SCA3 comes from haplotype of four different origins and was not from one origin in the Azores. Japan, Brazil and France all have been founder effects in areas with SCA3. Spinocerebellar ataxia type 3 (SCA3) on the Azores are believed to have come from Portugal's northeast where Sephardic Jews lived.Belgium, French-Guiana]] and Algeria have their own MJD mutation origins while Portuguese have two mutations, while MJD in Brazil and France have one origin, and Germans make up the majority of MHD patients in the United States. Azorean MJD suffers have their locus on the 14q24.3-32 chromosome, the same as some Japanese with MJD. It was an Azorean William Machado, whose offspring in New England were first to be diagnosed with MJD. The Azorean Californian Joseph family had MJD besides the Azorean Machados. The same origin for MJD is found in the Azores and in America's north-west coast. Not only Portuguese have it since African Americans, Indians, Italians and Japanese also developed MJD. In China the mutation causing type 3 has been estimated to have occurred 8,000 to 17,000 years ago. In Japan the oldest causative mutation appears to have occurred about 5774 +/- 1116 years ago.