Pelizaeus-Merzbacher disease

What causes Pelizaeus-Merzbacher disease?

Pelizaeus-Merzbacher disease is caused by mutations in the PLP1 gene. This gene provides instructions for producing proteolipid protein 1 and a modified version (isoform) of proteolipid protein 1, called DM20. Proteolipid protein 1 and DM20 are primarily located in the central nervous system and are the main proteins found in myelin, the fatty covering that insulates nerve fibers. A lack of proteolipid protein 1 and DM20 can cause dysmyelination, which can impair nervous system function, resulting in the signs and symptoms of Pelizaeus-Merzbacher disease.

It is estimated that 5 percent to 20 percent of people with Pelizaeus- Merzbacher disease do not have identified mutations in the PLP1 gene. In these cases, the cause of the condition is unknown.

Last updated on 05-01-20

How is Pelizaeus-Merzbacher disease inherited?

This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or may cause no symptoms at all. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the gene, but generally does not experience signs and symptoms of the disorder. Some females who carry a PLP1 mutation, however, may experience muscle stiffness and a decrease in intellectual function. Females with one PLP1 mutation have an increased risk of experiencing progressive deterioration of cognitive functions (dementia) later in life.

Individuals with a family history of Pelizaeus-Merzbacher disease may benefit from consulting with a genetics professional. This type of healthcare professional can provide information regarding genetic diagnosis, natural history, treatment, mode of inheritance, and genetic risks to other family members. Information about locating a genetics professional can be found under Healthcare Resources in the Find a Specialist section of this page.

Last updated on 05-01-20

What is Pelizaeus-Merzbacher disease?

Pelizaeus-Merzbacher disease is a disorder that affects the brain and spinal cord. It is a type of leukodystrophy and is characterized by problems with coordination, motor skills, and learning. The age of onset and the severity of the symptoms varies greatly depending on the type of disease. It is caused by an inability to form myelin due to mutations in the PLP1 gene. It is passed through families in an X-linked recessive pattern. The condition primarily affects males. Treatment requires a multidisciplinary team approach, with members dictated by the presenting symptoms.

Last updated on 05-01-20

What is the long-term outlook (prognosis) for individuals with Pelizaeus- Merzbacher disease?

The prognosis for those with Pelizaeus-Merzbacher disease is poor, with progressive deterioration until death. Individuals affected with the severe (connatal) type may die during infancy or childhood, usually of aspiration. With attentive care, these individuals may live into the third decade or longer. Survival into the sixth or seventh decade has been observed for individuals with the classic type.

Last updated on 05-01-20

How common is Pelizaeus-Merzbacher disease (PMD)?

It is estimated that between 1 in 200,000 to 1 in 500,000 people have PMD in the United states.

Last updated on 05-01-20

How might Pelizaeus-Merzbacher disease be treated?

There is no cure for Pelizaeus-Merzbacher disease, nor is there a standard course of treatment. Management typically involves a multidisciplinary team made of specialists in neurology, physical medicine, orthopedics, pulmonary medicine, and gastroenterology. Management tactics may include gastrostomy for individuals with severe dysphagia; antiepileptic drugs (AEDs) for seizures; and routine management of spasticity including physical therapy, exercise, medications (baclofen, diazepam, tizanidine, botulinum toxin), orthotics, and surgery for joint contractures. Individuals with scoliosis may benefit from proper wheelchair seating and physical therapy, with surgery reserved for the most severe cases. Specialized education and assessments are generally necessary, and assisted communication devices may be helpful.

Last updated on 05-01-20

Where To Start

MedlinePlus - Leukodystrophies

Medline provides a list of resources on leukodystrophies. MedlinePlus is a Web site designed by the National Library of Medicine to help you research your health questions.

Last updated on 04-27-20

Name: United Leukodystrophy Foundation (ULF) 224 North Second Street Suite 2
DeKalb, IL, 60115 , United States
Phone: 815-748-3211 Toll Free: 800-728-5483 Fax : 815-748-0844 Email: Url:
Name: Leukodystrophy Australia PO Box 2550 Mount Waverly
Victoria, 3149, Australia
Phone: 1800 141 400 Email: Url:
Name: The Myelin Project P.O. Box 39
Pacific Palisades, CA, 90272, United States
Phone: 800-869-3546; 806 356 4693 Fax : 806 356 4694 Email: Url:
Name: Association Européenne contre les Leucodystrophies (ELA) European Leukodystrophy Association 2, rue Mi-les-Vignes
BP 61024
54521 Laxou Cedex, France
Phone: 333 83 30 93 34 Fax : 333 83 30 00 68 Email: Url:
Name: Pelizaeus-Merzbacher Disease Foundation 1 Green Tree Center 1000 Lincoln Drive East, Ste 201
Marlton, NJ, 08053, United States
Phone: 609-443-9623 Email: Url:
Name: Alex The Leukodystrophy Charity Alex TLC 45 Peckham High Street
London, SE15 5EB, United Kingdom
Phone: 020 7701 4388 Email: Url:

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