Machado-Joseph Disease (MJD) belongs to a family of rare neurodegenerative condition that also includes Huntington’s disease. MJD is characterized by the progressive loss limb’s function, staggering movements, difficulty with speech and swallowing. The symptoms can be highly variable among the affected cases and typically develops during the 50s although it can affect young children. As this is a progressive condition, the symptoms deteriorate with time and the life expectancy of those with the early onset appears to be around mid-30s and the late onset can have a near-normal life expectancy. In most of the cases, the death occurs as the result of aspiration pneumonia. There are three types of MJD based on the age of onset and the symptoms that develop.
Causes
MJD is inherited ataxia of which there are several types and around 30 separate genetic mutation have been identified that causes the degeneration of the hindbrain cells. MJD belong to the disorders called expanded repeat diseases where the mutation presents abnormally long repeats of the DNA genetic code. Among the affected cases of MJD, the ‘CAG’ sequence is repeated in the gene known as ATXN3 which is responsible for the production of the protein called ataxin-3. The mutation causes the abnormal folding of the protein that accumulates in the brain cells known as inclusion bodies. MJD is inherited in an autosomal dominant pattern meaning the children of the parents who are carriers of the defective gene have 50% chance of developing the condition. Also, when the mutation typically extended is inherited by the children, the symptoms can develop more severely around 10 years earlier.
Symptoms
The type 1 MJD develops between the ages of 10 and 30 years which can continue to progress fast. The symptoms can include severe weakness of the limbs (dystonia), muscle rigidity or spasticity, staggering body movements, slurred speech, eye problems and difficulty swallowing. Type II presents symptoms similar to the type I and the age of onset are between 20 and 50 which progresses slowly. Type III occurs later in life, usually between 40 and 70 that presents the loss of muscle mass (amyotrophy). This is the slowest form of MJD that also includes insensitivity to pain, a problem with coordinating movement of the limbs and diabetes.
Diagnosis
The diagnosis is based on the identification of the associated symptoms and by assessing the individual’s family history. The molecular genetic testing is the only diagnosis that is highly accurate. Individuals with the risk of developing the condition based on their family history can have a presymptomatic test to determine whether they have the disease allele.
Treatment
There is no known cure for this disease although the symptoms can be treated. Levodopa therapy used to treat the symptoms associated with Parkinson’s can be helpful for several years. Antispasmodic medications can help by reducing spasticity. Speech problems can be treated with speech therapy and the eye condition may require the prism glasses that help reduce double vision. In some cases, physiotherapy can be beneficial with gait problems and walkers or wheelchairs can also help with their everyday activities.
References
https://rarediseases.org/rare-diseases/machado-joseph-disease/