Machado Joseph Disease
· Origins
of Machado Joseph Disease and the Jewish Connection
· What
is the Machado Joseph Disease?
· Symptoms
· How
is Machado Joseph Disease Inherited?
· How
is Machado Joseph Disease Diagnosed?
· Ongoing
Research Information
· You
Can Help
· Where
to Get Help
· Resources
and More
Origins of Machado Joseph Disease and the Jewish Connection
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.
What
is Machado Joseph Disease?
Joseph disease is a fatal 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. There
is as yet no effective treatment.
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
The disease progresses relentlessly and death occurs from 6 to 29 years after
onset.
How
is Joseph disease inherited?
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.
How
is the disease diagnosed?
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.
What
research is being done?
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.)
Where
to get help?
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
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
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