Machado-Joseph Disease

What is Machado-Joseph Disease?

Machado Joseph disease is a rare neurological disease that affects muscle control and contributes to gradual deterioration of brain cells in the hindbrain. It is also known as MJD, spinocerebellar ataxia type III, autosomal dominant spinocerebellar degeneration and Azorean neurologic disease.

It is common for patients with Machado Joseph disease to lose motor skills and abilities and even suffer from paralysis. Intellect is not usually affected.

Related disorders

There are three different types of Machado Joseph disease: type I, type II and type III. Related disorders that can cause similar symptoms include:

• Hallervorden-Spatz disease: this rare inherited condition affects the nervous system and results in impaired movement and muscle strength, a gradual loss of coordination, impaired cognition, speech problems and muscle spasms.
• Olivopontocerebellar atrophy: this is a rare group of disorders caused by damage to the cerebellum. Symptoms include muscle spasms, poor posture and slurred speech.
• PSP (progressive supranuclear palsy): this rare disorder affects the cranial nerves that control the facial muscles and the muscles in the throat. It tends to develop in middle age and is characterised by unsteadiness and an increased risk of falling. Symptoms progress with time and include loss of balance and difficulty swallowing.
• ALS (amyotrophic lateral sclerosis): this rare condition affects the motor neurons and results in a lack of strength in the muscles and gradual loss of coordination and movement. In the early stages, symptoms may include increased clumsiness and difficulty with fine motor movements.

What causes Machado Joseph disease?

Machado Joseph disease is genetic and research has linked it to 14q24.3-q31. Abnormalities on this gene affect CAG (cytosine, adenine and guanine) trinucleotides and the number of repeat sequences in the chain of DNA. Normally, there are between 12 and 43 CAG chains. However in cases of MJD, there are more, typically between 56 and 86. The number of copies varies according to the type of MJD. The more severe the case, the more copies are present.

MJD is inherited through a dominant pattern. Dominant conditions develop when only one defective gene is inherited. In recessive cases, a defective gene is required from both parents. This means that for every pregnancy, a child has a 50 percent chance of developing MJD.

What are the symptoms?

The types of MJD are classified according to the age of onset and the severity of signs.

MJD type I is the most severe form of the disease and tends to progress rapidly once symptoms develop between the ages of 10 and 30 years old. Symptoms include dystonia (a lack of strength in the limbs), a lack of muscle tone (hypotonia), slurred and slow speech and unsteady movement. Swallowing may be affected and it is common to experience problems with vision, which are caused by damage to the muscles around the eyes.

The symptoms of MJD type II are similar to those associated with type I, however progression is usually slower and symptoms develop between the ages of 20 and 50 years old. Type II MJD can affect the cerebellum region of the brain, which increases the risk of unsteadiness and a lack of coordination.

Type III MJD typically affects people over the age of 40 years old. It causes ataxia (unsteadiness) and is distinguished from other types of MJD by deteriorating muscle mass caused by swelling and deterioration of the peripheral nerves (this is known as motor polyneuropathy). Other symptoms include loss of sensation, lack of response to pain, lack of coordination and diabetes. With type III MJD, symptoms tend to develop gradually.

Who is affected?

Machado Joseph disease is rare. It affects males and females and is most common in people of Portuguese descent.

How is Machado Joseph disease diagnosed?

Genetic testing can be used to confirm the presence of additional CAG sequences.

Treatment for Machado Joseph disease

Treatment is not curative, but it can help to alleviate symptoms. Drugs, including L-dopa and baclofen, may be used to prevent spasms and reduce rigidity in the muscles. If you have family history of Machado Joseph disease, you may benefit from genetic counselling, especially if you are thinking of starting a family.