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At a glance

It is a rare hereditary neurodegenerative disorder, also called Spinocerebellar Ataxia Type III, which is characterized by weakness of arms and legs, spasticity, and a staggering lurching gait easily mistaken from drunkenness. Other clinical features include dysphagia, severe nystagmus, dystonia, and twitching of the tongue. Some patients have peculiar exophthalmos.

Synonyms

Spinocerebellar Ataxia Type III; Machado Disease; Joseph Disease; Portuguese-Azorean Disease; Azorean Neurologic Disease; Spinocerebellar Atrophy Type III; Spinopontine Atrophy; Nigro-Spino-Dental Degeneration.

History

In comparison with most other medical conditions, Machado-Joseph disease (MJD) is not named after researchers or clinicians that identified and described the syndrome. It is named after two men (“William Machado” and “Antoine Joseph”), who were the patriarchs of the families in which the condition was initially described. This medical condition was first described in 1972. In July 2016, Guilherme Karam, a comedian, actor, and TV personality in Brazil died of MJD. He had inherited the disease from his mother, like his brother and sister. Just days after his death, Arnaldo Duran, also a Brazilian personality, journalist, and television presenter, publicly acknowledged his affliction with MJD. Following these recognitions, the Brazilian press gave a huge attention for both cases and the disease in this country.

Classification

The differences in the types of MJD relate to the age of onset and severity.

  • Machado-Joseph Disease Type I (MJD-I): Characterized by age of onset between 10 and 30 years and presents a rapid evolution. Clinical features include a combination of dystonic and spastic muscle in the arms and legs, ataxia often associated with athetosis and dysarthria (as observed with drunkenness, slurred speech), ophthalmoplegia, and exophthalmia. Mental alertness and intellectual capacities are unaffected.

  • Machado-Joseph Disease Type II (MJD-II): Characterized by a symptomatology similar to that observed in Type I; however, the progression of the disease is slower. The age of onset is usually between 20 and 50 years. The distinctive characteristic of MJD-II is the presence of ataxia associated with increasing hypertonicity in the arms and legs, leading to significant difficulties in controlling movements.

  • Machado-Joseph Disease Type III (MJD-III): Characterized by a late onset between ages 40 and 70 years, severe ataxia, and slow degeneration of the central nervous system, particularly the hindbrain, motor polyneuropathy, and lateral amyotrophy. Individuals affected with this condition may become paralyzed early in their teens or during early adulthood. Individuals affected with this condition present with loss of feeling, lack of sensitivity to pain, impaired ability to coordinate movement of the arms and legs, and diabetes. The progression of type III disease is slowest of the three types.

  • Machado-Joseph Disease Type IV (MJD-IV): Distinguished from Parkinson because MJD responds to levodopa treatment.

  • Machado-Joseph Disease Type V (MJD-V): Appears to resemble Hereditary Spastic Paraplegia; however, the lack of research information preclude from establishing with certainty the relationship between both ...

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