Machado-Joseph Disease
Machado-Joseph disease, named for affected families of Azorean extraction, is a progressive neurologic disorder of genetic origin. Among Portuguese immigrants living in New England, this disease usually appears as an inherited ataxia (muscle movement disorder) occurring in descendants of William Machado, an Azorean native. Evidence from other families of Azorean origin living in Massachusetts and California has suggested that 4 reported kindreds (family related groups) had the same mutant gene despite differences in expression. The disorder begins as an ataxic gait after age 40. Some patients show air pockets in the lungs, muscle atrophy due to nerve damage, diabetes mellitus, features similar to those in Parkinson disease, limitation of eye movements, widespread fasciculations (twitching) of muscles, loss of reflexes in the lower limbs, and sometimes followed by mild cerebellar (brain) tremors. Medical examination of patients during life and after death who had similar disorders resulted in a scientific description of a group of diseases collectively described as Joseph disease and related to other families of Azorean origin. These two groups of diseases are now considered together as Machado-Joseph Disease.

It has been described that 28 families with Machado-Joseph disease are traceable to the Azorean Islands, mainly Flores and Sao Miguel, and 3 non-Azorean families in northeast Portugal. Machado-Joseph disease has been described in several families not known to be of Portuguese ancestry (e.g., an American black family originating from North Carolina, a family in Japan, and an Italian-American family). Because of the early influence of the Portuguese in Japan, the Japanese family may suffer from the same mutation as that in the Azorean cases. In addition a dominantly inherited form of ataxia resembling Machado-Joseph disease has been described in members of 4 families of the Arnhem Land Aboriginal people of northern Australia (Portuguese ancestry was possible, although not proven). In 1994, Machado-Joseph disease was reported in a family of Yemenite Jewish kindred that originated from a remote village named Ta'izz. This family, incidentally named Yoseph, had no documentation of Portuguese ancestry. Portuguese trade connections with the Yemenites most likely did not reach Ta'izz, which is far from the coast and is almost inaccessible because of a wall of high mountains.

In 1994 it was estimated that the prevalence of all forms of spinocerebellar degeneration is 4.53 per 100,000 population; of these, 2% were thought to have Machado-Joseph disease. Human DNA libraries have been screened and the nature of the exact gene is fairly well understood. Looking backward in the scientific literature this family of disorders is also known as;

SPINOCEREBELLAR ATAXIA 3; SCA3 SPINOPONTINE ATROPHY
SPINOCEREBELLAR ATROPHY III NIGROSPINODENTATAL DEGENERATION
AZOREAN NEUROLOGIC DISEASE ATAXIN 3, INCLUDED; ATX3, INCLUDED

For obvious reasons Machado-Joseph disease is the official charity of the Prince Henry Society of Massachusetts and is duly supported by the Taunton Chapter. Our support is directed at better understanding of the disease, its origins and treatment of patients regardless of national origin. If you would like more information, please contact one of our members, Prof. James T. Griffith, Ph.D., CLS (NCA) at JGRIFFITH@umassd.edu