SCA3MachadoJoseph

SCA3, also known as Machado-Joseph disease (MJD), is an autosomal dominant neurodegenerative disorder characterized by slowly progressive cerebellar ataxia and a variable mix of pyramidal signs, dystonia, parkinsonism, and neuropathy. It is caused by a CAG trinucleotide repeat expansion in the ATXN3 gene on chromosome 14, producing a toxic polyglutamine-containing ataxin-3 protein. Repeat length correlates with age at onset and severity; typical disease-causing alleles exceed about 55 repeats, with normal alleles usually below 44. The disorder was first described in 1972 by Machado and Joseph in families of Portuguese descent.

Clinically, onset is usually in adulthood with gait and limb ataxia, dysarthria, and nystagmus; many patients develop pyramidal signs, dystonia, or parkinsonism as the disease progresses.

Diagnosis is confirmed by genetic testing for ATXN3 CAG repeats. MRI may show cerebellar and brainstem atrophy.

There is no disease-modifying treatment; management is supportive and multidisciplinary, including gait and balance training, speech and occupational therapy, mobility aids, and treatment of symptoms such as spasticity or depression. Genetic counseling is advised due to autosomal dominant inheritance.

SCA3 is one of the more common spinocerebellar ataxias globally, with prevalence varying among populations.