Machado–Joseph disease

Autosomal dominant - en

Machado–Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is a rare, inherited neurodegenerative disorder that affects the central nervous system. It is characterized by progressive ataxia, a lack of muscle control and coordination, and other neurological symptoms. MJD is named after two families of Portuguese-Azorean descent, the Machado and Joseph families, in whom the disease was first identified.

Symptoms

The symptoms of Machado–Joseph disease vary widely among affected individuals but generally include:

• Ataxia: Loss of coordination and balance.
• Dystonia: Involuntary muscle contractions causing repetitive movements or abnormal postures.
• Spasticity: Increased muscle tone leading to stiffness and difficulty in movement.
• Dysarthria: Difficulty in articulating words.
• Ophthalmoplegia: Paralysis or weakness of the eye muscles.
• Peripheral neuropathy: Damage to the peripheral nerves causing weakness, numbness, and pain, usually in the hands and feet.

Genetics

Machado–Joseph disease is caused by a mutation in the ATXN3 gene located on chromosome 14. This gene mutation leads to an abnormal expansion of the CAG trinucleotide repeat, resulting in the production of an abnormal protein that accumulates in neurons, leading to cell death. MJD is inherited in an autosomal dominant manner, meaning that only one copy of the mutated gene is sufficient to cause the disorder.

Diagnosis

Diagnosis of Machado–Joseph disease is based on clinical evaluation, family history, and genetic testing. Magnetic resonance imaging (MRI) and computed tomography (CT) scans may be used to detect brain abnormalities associated with the disease.

Treatment

There is currently no cure for Machado–Joseph disease. Treatment focuses on managing symptoms and improving the quality of life for affected individuals. This may include:

• Physical therapy: To improve coordination and balance.
• Occupational therapy: To assist with daily activities.
• Speech therapy: To address speech and swallowing difficulties.
• Medications: To manage symptoms such as spasticity, dystonia, and neuropathic pain.

Prognosis

The progression of Machado–Joseph disease varies among individuals. Symptoms typically begin in mid-adulthood, but the age of onset can range from adolescence to late adulthood. The disease progresses over time, leading to increasing disability. Life expectancy may be reduced, but many individuals live for several decades after the onset of symptoms.

History

Machado–Joseph disease was first described in the 1970s in families of Portuguese-Azorean descent. The disease has since been identified in various populations worldwide, although it remains relatively rare.

See also

• Spinocerebellar ataxia
• Neurodegenerative disease
• Genetic disorder
• Ataxia telangiectasia
• Huntington's disease