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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.
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Spinocerebellar Ataxia Type III; Machado Disease; Joseph
Disease; Portuguese-Azorean Disease; Azorean Neurologic Disease;
Spinocerebellar Atrophy Type III; Spinopontine Atrophy; Nigro-Spino-Dental
Degeneration.
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The differences in the types of Machado-Joseph
disease (MJD) relate to the age of onset and severity.
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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.
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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.
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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.
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Machado-Joseph disease is one type of autosomal dominant
spinocerebellar ataxia. More than 100 families worldwide have been
described. Many of them live in the eastern United States and in Japan and
have ancestors from Portugal or the Azorean Islands. Estimated to be
0.1:100,000 persons in Japan.
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Machado-Joseph disease reflects a CAG triplet
expansion on chromosome 14q32.1. Studies of numerous kindreds suggest the
heterogeneous phenotypic expression of MJD may be related to the number of
CAG repeats. A phenomenon of anticipation is associated a higher number of
repeats with earlier onset.
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Histologically, degenerative changes with neuronal
loss and astrocytosis are seen in various loci of the cerebellum, midbrain,
brainstem, and medulla.
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Based on the clinical manifestations, family history,
and genetic analysis.
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Except for type I in which teens can begin to
show symptoms, the onset age of symptoms in MJD is most often during
adulthood. Manifestations of MJD are variable and include progressive
ataxia, dystonia, spasticity, facial and lingual fasciculations, bulbar
signs with impaired speech and dysphagia, and ocular findings, such as
bulging and injected ...