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Machado-Joseph Disease

Synonyms of Machado-Joseph Disease

  • Autosomal Dominant Spinocerebellar Degeneration
  • Azorean Neurologic Disease
  • Joseph Disease
  • Machado Disease
  • MJD
  • Nigrospinodentatal Degeneration
  • Spinocerebellar Ataxia Type III (SCA 3)
  • Striatonigral Degeneration, Autosomal Dominant Type

Disorder Subdivisions

  • Machado-Joseph Disease Type III (MJD-III)
  • Machado-Joseph Disease Type II (MJD-II)
  • Machado-Joseph Disease Type I (MJD-I)

General Discussion

Machado-Joseph Disease (MJD-III), also called spinocerebellar ataxia type III, is a rare, inherited, ataxia (lack of muscular control) affecting the central nervous system and characterized by the slow degeneration of particular areas of the brain called the hindbrain. Patients with MJD may eventually become crippled and/or paralyzed but their intellect remains intact. The onset of symptoms of MJD varies from early teens to late adulthood.

Three forms of Machado-Joseph Disease are recognized: Types MJD-I, MJD-II, and MJD-III. The differences in the types of MJD relate to the age of onset and severity. Earlier onset usually produces more severe symptoms.


The symptoms of MJD Type I present between the ages of 10 and 30 years and progress rapidly. They may include severe weakness in the arms and legs (dystonia), spasticity or muscle rigidity, (hypertonia), awkward body movements (ataxia) often involving a slow, staggering, lurching gait (athetosis) that may be mistaken for drunkenness, slurred speech and swallowing (dysarthria), and possible damage to the muscles that control eye movements (ophthalmoplegia) and bulging eyes (exophthalmia). Mental alertness and intellectual capacities are unaffected.

MJD-Type II symptoms are similar to those of Type I, but the disease progresses at a slower rate. Onset of Type II disease is usually between 20 and 50 years of age. The distinctive characteristic of Type II is increased dysfunction of the cerebellum that results in an unsteady gait (ataxia) and difficulty coordinating movements of the arms and legs, as well as spastic muscle movements.

MJD-Type III presents later in life, between years 40 and 70, and is characterized by an unsteady gait (ataxia) and is distinguished from the other forms of this disease by loss of muscle mass (amyotrophy) due to inflammation and degeneration of the peripheral nerves (motor polyneuropathy). Loss of feeling, lack of sensitivity to pain, abnormal sensations, impaired ability to coordinate movement of the arms and legs, and diabetes are also common. The progression of Type III disease is slowest of the three types.

A number of the symptoms, and their appearance in combination, resemble the symptoms of other neurologic disorders such as Parkinson's disease or multiple sclerosis. A proper diagnosis is therefore difficult and should be the responsibility of an experienced neurologist.


The gene responsible for MJD has been identified and mapped to Gene Map Locus; 14q24.3-q31. This gene is associated with an abnormal number of CAG trinucleotide repeats (sometimes called triplets) in the DNA. (CAG refers to the Cytosine-Adenine-Guanine trinucleotide structure.) "Normal" DNA usually has between 12 and 43 copies of the CAG trinucleotide. In persons with the disease, the DNA contains from 56-86 copies of this trinucleotide. Severity of symptoms and age of onset are related directly to the number of the repeats. Thus, MJD-I will have fewer of these triplets while MJD-III will have the greater number. The number of the CAG triplets found in the DNA of patients with MJD-II lies between the two extremes.

MJD is inherited as an autosomal dominant trait. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 11p13" refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Affected Populations

MJD is a rare inherited neurological disorder that disproportionately affects individuals of Portuguese descent, especially those from the Azores, an island colonized by Portuguese people. MJD appears to affect slightly more males than females.

Related Disorders

Symptoms of the following disorders can be similar to those of Machado-Joseph Disease. Comparisons may be useful for a differential diagnosis:

Hallervorden-Spatz Disease is a rare inherited disorder characterized by neurological degeneration. Symptoms may include slow, steady muscle contractions of the arms, legs, neck, face, mouth, or trunk. Other symptoms may include muscle spasms, slurred speech (dysarthria), mental retardation, impaired speech (dysphasia), and the loss of muscle mass (amyotrophy). (For more information on this disorder choose "Hallervorden-Spatz" as your search term on the Rare Disease Database.)

Olivopontocerebellar Atrophy is a group of rare inherited neurological disorders characterized by progressive neurological degeneration. These diseases effect the brain (outer layers of cerebellum) and result in impaired ability to coordinate movement (ataxia). Symptoms vary and may include muscle spasms, involuntary movements, abnormal posture, slurred speech (dysarthria), and changes in muscle tone (extrapyramidal signs). The symptoms and age of onset vary according to the type of Olivopontocerebellar Atrophy. (For more information on this disorder, choose "Olivopontocerebellar Atrophy" as your search term on the Rare Disease Database.)

Progressive Supranuclear Palsy (PSP) is a rare neurological disorder characterized by spastic weakness of muscles controlled by the cranial nerves (i.e., face, throat and tongue). The symptoms usually begin during middle age and may include loss of balance while walking, a stiff gait (ataxia), or unexplained falls. Different symptoms can develop during the course of this disorder, and previously mild problems may become more severe with time. (For more information on this disorder, choose "Progressive Supranuclear Palsy" as your search term on the Rare Disease Database.)

Amyotrophic Lateral Sclerosis (ALS) is a rare disease of the skeletal muscle nerve cells (motor neurons). It effects the motor neurons that control the upper and lower parts of the body and results in muscle weakness and the progressive wasting of muscles. The early symptoms of Amyotrophic Lateral Sclerosis may include muscle weakness, clumsy hand movements, and difficulty performing tasks that require delicate movements of the fingers and hands. Other symptoms may include weakness of the muscles of the lips, tongue, mouth, and voice. (For more information on this disorder, choose "Amyotrophic Lateral Sclerosis" as your search term in the Rare Disease Database.)

Friedreich's Ataxia is a rare inherited disorder characterized by degenerative changes and the progressive deterioration of the brain and spinal cord. Symptoms may include muscle weakness and numbness in the arms and legs, curvature of the spine (secondary lateral scoliosis), and paralysis of the legs. (For more information on this disorder, choose "Friedreich's Ataxia" as your search term in the Rare Disease Database.)

Marie's Ataxia is a rare inherited neurological disorder characterized by progressive loss of muscle coordination and an awkward, unsteady gait (ataxia). Progressive spinal nerve degeneration leads to the loss of muscle mass (amyotrophy) in the arms, legs, head, and neck. (For more information on this disorder, choose "Marie's Ataxia" as your search term in the Rare Disease Database.)

Parenchymatous Cortical Degeneration of the Cerebellum is a rare neurological disorder characterized by the progressive deterioration of areas of the brain which coordinate movement and muscle coordination. This disease may be inherited or acquired. Symptoms may include slurred speech and a halting, unsteady gait (ataxia). (For more information on this disorder, choose "Parenchymatous Cortical Degeneration" as your search term in the Rare Disease Database.)

Standard Therapies

While a family history and physical examination help in the diagnosis, the gold standard of diagnostic tests that detects 100% of the cases is the direct determination of the number of suspect CAG triplets in a patient's DNA. This may be readily done at a specialized genetic clinical laboratory.

Treatment is symptomatic and supportive. The drugs L- dopa and baclofen may relieve muscle rigidity and spasticity. Individuals with at least one family member who has been diagnosed with this disease should consider genetic counseling.

Investigational Therapies

Information on current clinical trials is posted on the Internet at All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010

For information about clinical trials sponsored by private sources, contact:

Machado-Joseph Disease Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at

Other Organizations:


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The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2008/05/23 00:00:00 GMT+0

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