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Machado Joseph Disease
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Description
Joseph disease is a fatal autosomal
dominant genetic disorder of the nervous system that cripples
and paralyzes while leaving the intellect intact. The disease is characterized
by weakness in the arms and legs and a general loss of motor control that
eventually confines the patient to a wheelchair.
Symptoms appear when a defective gene causes a breakdown and loss of cells in
a specific areas of the brain known as the striatum, the cerebellum, and the
substantia nigra, but what sets this process in motion is still unknown.
Machado Joseph disease, first documented
in the 1970's, is named for Antone Joseph, a Portuguese sailor with
the defective gene who came to California in 1845. The disease
occurs primarily in people of Portuguese ancestry, but it has also
been found in other ethnic groups, nationalities, and races.
At least two Brazilian families originated in mainland Portugal, and
another one claims to descend from Portuguese Jews in Amsterdam.
Another affected family migrated directly from northeastern Portugal
to the United States.
Taking into account the family names and traditional professions,
physical phenotype, and places of residence of the affected families
in mainland Portugal and of the Bastiana (Joseph) family, it is
suggested that the original MJD mutation may have arisen among the
settlements of Sephardic Jews in northeastern Portugal. The
Sephardic Jews, having arrived on the Iberic peninsula mainly with
the Moorish invasions, later came to Portugal seeking refuge from
imminent expulsion from Spain in 1492, and they settled mainly along
the Spanish-Portuguese border, subject to varying periods of
tolerance and repression. When forced conversion or expulsion was
decreed also in Portugal in 1496, most of the Jews chose to stay and
had to practice their faith in secret or assimilate. Mixed religious
practices and cultures can still be found in those areas, although
local Sephardic communities can no longer be well identified.
Interestingly, many of the Portuguese with MJD, both in Portugal and
the United States, still bear family names traditionally attributed
to the Sephardim.
Symptoms
Some symptoms of Joseph disease resemble those of other neurological
disorders such as multiple sclerosis and Parkinson's disease. A
careful diagnosis is therefore important and should be made by a
physician with expertise in neurology. Symptoms of Joseph disease
include:
· Weakness in the arms and legs
· Spasticity, especially in the legs
· Awkward body movements
· Staggering, lurching gait-easily
mistaken for drunkenness
· Difficulty with speech and swallowing
· Involuntary eye movements
double vision
· Bulging appearance of the eyes
· Frequent urination
Joseph disease is diagnosed by identifying the typical symptoms in a family in
which the disease occurs. Characteristic features include progressive difficulty
in walking an speech beginning in the late teen years or in the 20's through the
50's. The gait is abnormal due to spasticity and speech is slurred because of
spastic weakness in the throat muscles. The Joseph disease patient may be unable
to look upward or inward, and the eyes may oscillate from side to side.
Late-onset Joseph disease, the type that begins when a patient is 70 or older,
is characterized by an uncoordinated gait that may cause the patient to stumble
or fall, the slurring speech, and the loss of muscle in the arms and legs.
Neurologists have classified Joseph disease into three types, depending on age
at onset and characteristic symptoms. But it is uncertain whether the three
types are subtypes of the same disease or three separate diseases. Because the
three types have at times borne different names, the plural term Joseph diseases
has been used.
The disease progresses relentlessly and death occurs from 6 to 29
years after onset.
Incidence and Carriers
Joseph disease is an autosomal dominant disorder. This means that
each child of an affected parent has a 50 percent chance of
inheriting the defective gene. Joseph disease does not skip
generations, but people at risk who escape the disease will not pass
it on to their children or future generations. People at risk must
decide whether to have children without knowing for sure whether
they might pass the gene on. As with any inherited disorder, Joseph
disease is not contagious and cannot be "caught" by people who are
not at risk.
Treatment
Currently there is no cure for Machado Joseph Disease, but some
symptoms of the disease can be treated. Spasticity as well as sleep
disturbances can be treated with medications. Physical therapy can
help patients with gait disturbances.
Testing
The National Institute of Neurological and Communicative Disorders
and Stroke (NINCDS) conducts and supports research on all disorders
of the nervous system, including Joseph disease. Much of this
research is relevant to different aspects of Joseph disease, and may
lead to treatment, a cure, and eventually prevention.
NINVDS is studying normal and defective genes to understand how
inherited characteristics are transmitted. With such knowledge and
improved genetic engineering techniques, intervention and a cure for
inherited disorders like Joseph disease might be possible.
A number of other neurological disorders share symptoms with Joseph
disease, and research conducted on these disorders should benefit
Joseph disease patients. NINCDS scientists are studying the
degeneration of the brain's cerebellum that occurs in the ataxias.
This type of degeneration produces the kind of spasticity and tremor
seen in Joseph disease. NINCDS research on motor neuron diseases,
including amyotorphic lateral sclerosis and spastic paraplegia,
focuses on the deterioration of certain nerve cells in the spinal
cord that also degenerate in Joseph disease.
Much NINCDS-supported research on Parkinson's disease is relevant to
Joseph disease. The brain's substantia nigra area is under study
because it deteriorates in both disorders. The development of drugs
that will increase dopamine-a brain chemical missing in Parkinson's
disease-may produce an effective therapy for symptoms of Joseph
disease. Investigators using a special imaging technique called
positron emission tomography (PET) have already produced the first
pictures of dopamine at work in the living brain. Further studies
with PET may increase our understanding of dopamine's possible
connection to Joseph disease.
Some scientists are studying the role of enzymes in
olivonpontocerebellar atrophy, a rare inherited neurological
disorder similar to Joseph disease. These studies may uncover an
enzyme defect that could also be responsible for Joseph disease.
Some patients with Joseph disease have high blood glucose levels and
abnormal glucose tolerance
test
results. Research has also shown that some patients have reduced
levels of homovanillic acid (a nervous system chemical) in their
spinal fluid. These abnormalities are of special interest to
scientists studying Joseph disease.
The National Institute of Neurological
and Communicative Discords and Stroke and the National Institute of
Mental Health support two national human brain specimen banks, one
at the Wadsworth Veterans Administration Hospital in Los Angeles and
the other at McLean Hospital near Boston. These banks supply
investigators around the world with tissue from patients with
neurological and psychiatric diseases. Both banks need brain tissue
from Joseph disease patients to enable scientists to study this
disorder more intensely. Prospective donors would write to:
Dr. Wallace W. Tourtellotte, Director
Human Neurospecimen Bank
VA Wadsworth Medical Center
Building 212, Room 31
Los Angeles, Ca 90073
Telephone: 213-824-4307 (Call Collect)
Dr. Edward D. Bird, Director Brain Tissue Bank, Mailman Research
Center McLean Hospital 115 Mill Street Belmont, Massachusetts 02178
Telephone (617) 885-2400 (Call collect 24 hours a day.)
Resources and More
International Joseph Diseases Foundation, Inc.
Executive Director: Sheri Bashor
P.O Box 994268
Redding, CA 96064
Telephone: 530-246-4722
Telephone: 530-232-2773
Email: MJD@ijdf.net
Website: http://www.ijdf.net
Ataxia MJD Research Project, Inc.
875 Mahler Road, Suite 161
Burlingame, CA 94010-1621
Telephone: 650-259-3984
Fax: 650-259-3983 fax
Email:Ldenning@ataxiamjd.org
Website: http://www.ataxiamjd.org
For additional information concerning Joseph disease research supported by the
National Institute of Neurological and Communicative Disorders and Stroke,
contact:
Office of Scientific and Health Reports
National Institute of Neurological and Communicative
Disorders and Stroke
Building 31, Room 8A-06
National Institutes of Health
Bethesda, Maryland 20892
Telephone: 301-496-5751
Support Groups
The International Joseph Diseases Foundation is a voluntary, nonprofit
organization of concerned people including patients, their families and friends,
and health- care professionals. The foundation provides information about the
disease, supports and conducts clinical research, and helps patients find
medical, social, and genetic counseling services.
International Joseph Diseases Foundation, Inc.
P.O. Box 2550
Livermore, California 94550 |
