Machado-Joseph Disease and the Spinocerebellar Ataxias Fact Sheet

man standing with a cane in a city

Machado-Joseph Disease and the Spinocerebellar Ataxias Fact Sheet

Photo by Sunguk Kim on Unsplash

 

What is spinocerebellar ataxia? What is Machado-Joseph Disease?

What are the symptoms of SCA?

What are the most common forms of SCA?

What causes spinocerebellar ataxia?

How is SCA diagnosed?

How is SCA treated?

What research is being done?

Where can I get more information?


 

What is spinocerebellar ataxia? What is Machado-Joseph Disease?

Spinocerebellar ataxia (SCA) refers to a group of rare genetic neurological disorders that cause loss of muscle control, coordination, and balance. The SCAs involve loss of structure and function (degeneration) of the cells of the hindbrain, which includes the cerebellum (the part of the brain that helps control muscle movement and balance), the brain stem and upper part of the spinal cord, and sometimes other parts of the nervous system. There are more than 30 distinct types of SCA, which are numbered in order of the discovery of the gene mutation that causes each type. The term “spinocerebellar ataxia” refers to those ataxias that are inherited in an autosomal dominant manner (see “What causes SCA?”, below). Machado-Joseph Disease (SCA3) is one of these disorders.

The types and severity of symptoms vary among these ataxias. SCA is progressive, meaning the symptoms worsen with time. Some forms of SCA may progress slowly over a period of years, while others worsen within months. Generally, people with SCA will require a wheelchair within 10 to 20 years of diagnosis. SCA can be fatal but some people with the disease have a normal life span. 

 

What are the symptoms of SCA?

Depending on the type of SCA, symptoms appear most often in adulthood but can appear in childhood. Several SCAs may have their own clinical signs, but most include:

  • Progressive loss of coordination and balance
  • Progressive lack of coordination in the arms and legs, including tremor
  • Slowness of movement
  • Problems with walking (gait)
  • Decreased muscle tone
  • Vision problems, particularly with focusing the eyes and unwanted eye movements
  • Difficulty with speaking (dysarthria) and swallowing (dysphagia)
  • Problems with thinking, remembering, and concentration

 

What are the most common forms of SCA?

The most common forms of SCA are types 1, 2, 3, and 6, which account for most of the disorders.

SCA1 involves weakness and paralysis of the muscles of the eye and eyelid, blurred and double vision, and problems with moving the eyes. There will be ataxia—the loss of control and coordination of muscles we can willingly move—of the arms and legs, and problems speaking and swallowing. Other symptoms may include muscle stiffness (spasticity), peripheral neuropathy (damage to or loss of signaling of the nerves that connect the brain and spinal cord to the rest of the body), and overactive muscle reflexes. Individuals with SCA1 may have difficulty processing, learning, and remembering information (cognitive impairment). Disease onset is usually between 30 and 40 years of age but can appear much earlier or later.

SCA2, also called olivopontocerebellar atrophy, involves problems with vision and eye muscle control and degeneration of the retina (the light-sensing part of the eye). Additional symptoms may include peripheral neuropathy, tremor, muscle wasting (atrophy), and brief unplanned twitching of a muscle or group of muscles (myoclonus). People with SCA2 also may have problems with short-term memory, planning, and problem solving, or experience an overall decline in intellectual function (dementia). Depending on its severity, SCA2 can have disease onset as early as infancy through adulthood.

SCA3, also called Machado-Joseph Disease (MJD), is characterized by slowly progressive clumsiness in the arms and legs, a staggering lurching gait, difficulty with speech and swallowing, impaired eye movements sometimes accompanied by double vision or bulging eyes, and lower limb spasticity. Some individuals develop dystonia (sustained muscle contractions that cause twisting of the body and limbs, repetitive movements, and abnormal postures) or symptoms similar to those of Parkinson’s disease such as slowness of movement and muscle stiffness (rigidity). Others may develop twitching of the face or tongue, neuropathy, sleep disorders, or problems with urination and the autonomic nervous system (which regulates body functions such as breathing, digestion, heart rate, and blood pressure). Cognitive impairments can include problems speaking and remembering.

There are different types of MJD:

  • Type I is characterized by onset between about 10 and 30 years of age, with faster progression and more dystonia and rigidity than ataxia.
  • Type II, the most common type, generally begins between the ages of about 20 and 50 years, has an intermediate rate of progression, and causes various symptoms, including prominent ataxia, spastic gait, and enhanced reflex responses. 
  • Type III has the latest onset of disease (beginning between approximately 40 and 70 years of age) which progresses relatively slowly and is characterized as much by peripheral neuromuscular involvement (muscle twitching, weakness, atrophy, and abnormal sensations such as numbness, tingling, cramps, and pain in the hands and feet) as by ataxia. 

Most individuals with MJD, but especially those with types I and II, experience one or more problems with vision, including double vision or blurred vision, loss of ability to distinguish color and/or contrast, and inability to control eye movements. Some individuals also experience prominent Parkinson’s disease-like symptoms such as slowness of movement, rigidity or stiffness of the limbs and trunk, and tremor or trembling in the hands.

SCA6 involves ataxia, problems walking, problems speaking, and involuntary side to side, up and down motions of the eyes that may include limited or reduced vision. Other symptoms may include peripheral neuropathy, decreased vibration, problems with sense perception, spasticity, exaggerated reflexes, and problems moving the eyes. SCA6 generally begins between the ages of 20 and 50 years and progresses slowly.

 

What causes spinocerebellar ataxia?

SCA is passed from parent to child in an autosomal dominant pattern, meaning that only one parent needs to carry the gene mutation that causes signs or symptoms of the disease (genes come in pairs, with one copy inherited from each parent). A mutation causes a gene to make abnormal proteins that impair nerve cell function. When a parent has SCA, each child has a 50 percent chance of inheriting the mutated gene and, if so, will eventually develop symptoms of the disease. A child who does not inherit the SCA mutation will not develop the disease and cannot pass it to future generations. 

SCAs belong to a class of genetic disorders called expanded repeat diseases. People with SCA have an abnormal, repetitive, greatly expanded three-letter code (or triplet) in the DNA sequence that is found in genes. DNA uses triplets to prescribe the order and identity of amino acids—a protein’s building blocks. This three-base repeat—called a triplet repeat expansion—causes many other neurological diseases. These repeat expansions can vary greatly in size, even among affected persons in the same family. Longer repeat expansions tend to cause more severe disease that begins earlier in life and shows a broader range of neurological symptoms.

One unusual feature of SCA and many other expanded repeat diseases is a phenomenon called anticipation, in which the signs and symptoms of some genetic conditions tend to become more severe and appear at an earlier age as the disorder is passed from one generation to the next. This is due to the tendency for the expanded repeat mutation to further expand when being passed to the next generation, especially when passed from the father. 

 

How is SCA diagnosed?

Physicians diagnose SCA through various neurological tests and by taking a family history of any disease. They ask detailed questions about family members who show (or showed) symptoms of the disease, the kinds of symptoms seen in these relatives, the age(s) of disease onset, and the progression and severity of symptoms. Neuroimaging, using computed tomography and magnetic resonance imaging, can show atrophy of the cerebellum and other brain structures. Other forms of imaging can show changes in brain function.

A definitive diagnosis of SCA can be made only with a genetic test. Genetic testing can confirm mutations of a known gene to cause SCA. The genetic test for MJD (SCA3) is highly accurate. Those individuals who are at risk for MJD or another SCA (for example, those who have an affected parent) but do not have any symptoms can undergo presymptomatic testing to determine whether they carry the gene mutation (and therefore will likely later develop the disease). Genetic testing is voluntary. Because testing has benefits as well as limitations and risks, the decision about whether to be tested is a personal and complex one. A geneticist or genetic counselor can help by providing information about the pros and cons of the test and discussing the social and emotional aspects of testing. For more information on genetic testing, see MedlinePlus: What is genetic testing?

 

How is SCA treated?

There is no definitive treatment to cure SCA or slow its progression, but some symptoms of the disease can be treated. 

  • Coordination and balance can be assisted by using physical aids such as canes, walkers, crutches, and wheelchairs to help with everyday activities and maintain independence.
  • Special glasses can reduce blurred or double vision. Eye surgery has only short-term benefits due to the progressive degeneration of eye muscles.
  • Stiffness and slowness of movement can be treated using levodopa therapy (used in treating individuals with Parkinson’s disease), but the benefit may be limited. Antispasmodic drugs, such as baclofen, can help reduce spasticity. Botulinum toxin can treat severe spasticity and some symptoms of dystonia, but has possible side effects, such as swallowing problems (dysphagia). 
  • Speech and swallowing problems can be treated with medication and speech therapy. Computer devices can assist individuals with severe speech difficulties.
  • Maintaining strength and movement can be aided by physical therapy. Physiotherapy can help individuals cope with disability associated with gait problems.
  • Daytime sleepiness, a common complaint in Machado-Joseph Disease (as is sleep disturbance in general), can be treated with medicines and should call for a formal sleep evaluation. 
  • Other problems, such as cramps and urinary dysfunction, can be treated with medications and medical care. Occupational therapy can help individuals learn ways to better perform daily tasks such as feeding and bathing.

 

What research is being done?

The National Institute of Neurological Disorders and Stroke (NINDS) supports research on SCAs including MJD in an effort to learn how to better treat, prevent, and even cure these diseases. Ongoing research includes efforts to better understand the genetic, molecular, and cellular mechanisms that underlie repeat expansion diseases related to SCAs including MJD, and other abnormal triplet repeat expansion diseases.

Overlapping mechanisms may be involved in triplet repeat disorders such as MJD, regardless of whether or not the repeat is in a protein-producing or coding region of the gene. Modifications of the mutant protein can impact toxicity, which may explain why some triplet repeat diseases have onset later in life.

Clinical trials include investigating treatments for SCAs including MJD, identifying biomarkers (signs that can be used to diagnose a disease and monitor its progression), a natural history study of and genetic modifiers in the SCAs, and developing a patient registry for rare diseases, including the SCAs, to allow individuals with these disorders and researchers to connect as easily as possible to help advance treatments and cures for rare diseases including the spinocerebellar ataxias.

Other research includes work to better understand the molecular mechanisms involved with SCAs, improve current diagnostic procedures, and develop disease-modifying and other therapies for the spinocerebellar ataxias.

More information on NIH efforts on SCA research and on other disorders can be found using NIH RePORTER, a searchable database of current and past research projects supported by NIH and other federal agencies. RePORTER also includes links to publications and patents citing support from these projects.

 

Where can I get more information?

For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

BRAIN

P.O. Box 5801

Bethesda, MD 20824

800-352-9424

Information also is available from the following organizations:

National Ataxia Foundation (NAF)

600 Highway 169 South, Suite 1725

Minneapolis, MN 55426

naf@ataxia.org

Tel: 763-553-0020

Fax: 763-553-0167

National Organization for Rare Disorders (NORD)

55 Kenosia Avenue

Danbury, CT 06810

orphan@rarediseases.org

Tel: 203-744-0100; Voice Mail: 800-999-NORD (6673)

Fax: 203-798-2291

Dystonia Medical Research Foundation

1 East Wacker Drive

Suite 1730

Chicago, IL 60601-1980

dystonia@dystonia-foundation.org

Tel: 312-755-0198

Fax: 312-803-0138

National Aphasia Association

P.O. Box 87

Scarsdale, NY 10583

naa@aphasia.org

Tel: 212-267-2814; 800-922-4NAA (4622)

Fax: 212-267-2812

American Speech-Language-Hearing Association (ASHA)

2200 Research Boulevard

Rockville, MD 20850

actioncenter@asha.org

Tel: 800-638-8255

Fax: 301-571-0457

Genetic Alliance

26400 Woodfield Road #189

Damascus, MD 20872

info@geneticalliance.org

Tel: 202-966-5557; 800-336-GENE (4363)

Fax: 202-966-8553

 


Online information updated June 7, 2021

"Machado-Joseph Disease Fact Sheet", NINDS, Publication date February 2010.

NIH Publication No. 10-2716

Back to Machado-Joseph Disease Information Page

See a list of all NINDS Disorders


Publicaciones en Español

Enfermedad de Machado-Joseph


Prepared by:

Office of Communications and Public Liaison

National Institute of Neurological Disorders and Stroke

National Institutes of Health

Bethesda, MD 20892

NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.

All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.

 

Source: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Machado-Joseph-Disease-Fact-Sheet

Capture Date: September 8, 2021

 

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