What is Pelizaeus-Merzbacher Disease?

Pelizaeus-Merzbacher Disease, or PMD, is a genetic disorder that affects the central and peripheral nervous systems.

Jack Leonard (3/9/00 - 6/20/15) - Pelizaeus-Merzbacher Disease

PMD is part of a group of genetic disorders called Leukodystrophies. Leukodystrophies are characterized as diseases that cause deterioration of the myelin (sometimes referred to as white matter) in the brain. PMD is caused by an inability to form myelin due to a defect in the Proteolipic Protein (PLP1) gene.

PLP is used by cells in the brain to make myelin in the central and peripheral nervous systems. This is the most prominent protein found in myelin. Without the correct amount of PLP in the brain, the body’s production of myelin becomes impaired or nonexistent. The deterioration of the myelin sheath interrupts signals sent and received from the central and peripheral nervous systems, resulting in progression of the disease.

Those affected by PMD may become symptomatic at birth or may appear healthy until they experience symptoms of the disease. In most cases, symptoms usually appear within the first year of life.

How does PMD affect the individual?

The central nervous system is made up of the nerves within the brain and spinal cord and is the primary control center of the body. The peripheral nervous system’s primary function is to carry information from the brain and spinal cord throughout the body to the limbs and organs.

PMD affects both the central and peripheral nervous systems. Individuals affected by PMD have an abnormality on the PLP1 gene on the X chromosome, which disrupts the production of myelin. Myelin is the insulating sheath that surrounds and protects the nervous system and is needed for the rapid transmission of information to and from neurons throughout the body. Communication with the brain and nervous system becomes restricted or lost, resulting in progression of the disease.

Some symptoms an individual affected by PMD may experience could include but is not limited to muscle weakness, nystagmus (rapid, involuntary movement of the eyes), delays in motor development, feeding difficulties, breathing difficulties, muscle spasms, seizures, impaired cognition, dysarthria (speech difficulties), and lack of head control.

The rate of progression depends on what form of the disease the individual has, however, as PMD advances, it encompasses all aspects of bodily function and is a fatal disorder.

Although there is currently no cure for PMD, it is treatable. With proactive, comprehensive medical care the symptoms of PMD can be well-managed to give the individual the best quality of life possible.

How do you get PMD?

PMD is an X-linked disorder, meaning the mutated gene that causes the disorder is located on the X chromosome.

At birth females receive two X chromosomes while males receive one X and one Y chromosome. If females inherit the altered gene on one of the X chromosomes, the other X chromosome is able to compensate for the defect. However, if males inherit the defected gene, there is not an extra X chromosome to counteract the disease-causing, altered gene.

Another characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons, however, a female carrier with one altered copy of the gene can pass it on and generally will not experience signs and symptoms.

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.

X-Linked Pelizaeus-Merzbacher Disease

Could other children in the family also have PMD?

When the mother is a carrier, each child has a 1 in 2 chance of being affected, and daughters have a 1 in 2 chance of being a carrier. To determine if other children in the family are affected by PMD, it is best to consult with your genetic counselor or your child’s physician.

How is PMD diagnosed?

PMD is diagnosed through clinical evaluation MRI, CT and can be confirmed through genetic testing since the responsible, disease-causing gene is known. Carriers can also be identified through genetic testing.

What are the different forms of PMD?

No matter what form of PMD an individual is diagnosed with, optimal care is of timely importance. The Leukodystrophy Care Network (LCN) was established to provide individuals with the best quality of care at specialized centers across the country.

For more information and to find a Leukodystrophy Care Center nearest you, please visit the Leukodystrophy Care Network page.

There are two different forms of PMD, Classic and Connatal. Although the two forms differ in severity, their features overlap.

Classic Pelizaeus-Merzbacher Disease

Classic Pelizaeus-Merzbacher Disease is the more common type between the two. Within the first year of life, those affected with Classic PMD typically experience weak muscle tone (hypertonia), involuntary movements of the eyes (nystagmus), and delayed development of motor skills such as crawling or walking.

As the child gets older, nystagmus usually stops, but other movement disorders develop, including muscle stiffness (spasticity), problems with movement and balance (ataxia), and involuntary jerking (choreiform movements). Most individuals who experience Classic PMD will usually live into mid-adulthood.

Connatal Pelizaeus-Merzbacher Disease

Connatal Pelizaeus-Merzbacher Disease is the more severe of the two types. Symptoms can begin in infancy. Some of the symptoms include, but are not limited to, problems feeding, a whistling sound when breathing, progressive spasticity leading to joint deformities (contractures) that restrict movement, speech difficulties (dysarthria), ataxia, and seizures.

Those affected with Connatal Pelizaeus-Merzbacher Disease show little development of motor skills and intellectual function with death usually occurring within the first decade of life.

Is there a treatment for PMD?

There are some therapy, drug and surgery interventions that are effective in management of symptoms to improve a patient’s quality of life and lifespan. In some cases where symptoms are not prominent, an affected individual may qualify for an umbilical cord blood or bone marrow transplant to stop the progression of the disease.

For a cord blood transplant, stem cells come from umbilical cords that are donated and stored after live, healthy births of unaffected donors. To learn more about donating your baby’s umbilical cord, please visit the Carolina Cord Blood Bank.

Even when a transplant is not an option, the symptoms of PMD can be managed. 

There is no cure for PMD; however, with proactive, comprehensive medical care, affected individuals can avoid unnecessary suffering and complications to have the best quality of life possible. For more information, visit the Leukodystrophy Care Network page.

What if my child was diagnosed too late for transplant?

If an individual is not eligible for transplant, proactive multidisciplinary care is essential to provide the best quality of life possible. There are a variety of therapies, adaptive equipment, and medications available for this very purpose.

All families and caregivers of individuals affected by Leukodystrophy, whether they qualify for transplant or not, should seek expert care through the Leukodystrophy Care Network, or LCN.

What research is being done to find better treatments & a cure for PMD?

Hunter’s Hope is committed to funding research for better treatments and a cure for Leukodystrophies. To learn more about the groundbreaking research currently underway, visit the Research section of our website.

The PMD Foundation is committed to funding research for better treatments and a cure for PMD and other Leukodystrophies. To learn more about the groundbreaking research currently underway, visit the PMD Foundation website.

The PMD Foundation is also committed to research. You can find out more by visiting the PMD Foundation website.

Additional Resources for Families

Hunter’s Hope Foundation – Family Care
Hunter James Kelly Research Institute
Duke Children’s Hospital: Bone Marrow and Stem Cell Transplantation

Additional Resources for Medical Professionals

NIH Gene Reviews: Pelizaeus-Merzbacher Disease
NIH National Institute of Neurological Disorders and Stroke: Pelizaeus-Merzbacher Disease
NIH National Center for Advancing Translational Sciences, Genetic and Rare Disease Information Center: Pelizaeus-Merzbacher Disease
NIH Genetics Home Reference, Your Guide to Understanding Genetic Conditions: PLP1 gene

A Special Thank You

Thank you to Don Hobson from the PMD Foundation for the content provided on this page.