Pelizaeus–Merzbacher disease

X-linked recessive (carrier mother)

Pelizaeus–Merzbacher disease (PMD) is a rare, progressive, degenerative central nervous system disorder in which coordination, motor abilities, and intellectual function deteriorate. It is one of a group of genetic disorders known as leukodystrophies, which are characterized by the degeneration of myelin, the fatty covering that insulates nerve fibers in the brain and spinal cord.

Classification

Pelizaeus–Merzbacher disease is classified into several types based on the severity and age of onset:

• Classic PMD: The most common form, presenting in early infancy.
• Connatal PMD: A more severe form, presenting at birth or shortly thereafter.
• Transitional PMD: Intermediate severity, with symptoms appearing in late infancy or early childhood.
• Adult PMD: A rare form with symptoms appearing in adulthood.

Symptoms

The symptoms of PMD vary depending on the type but generally include:

• Nystagmus (involuntary eye movement)
• Hypotonia (reduced muscle tone)
• Ataxia (lack of muscle coordination)
• Spasticity (stiff or rigid muscles)
• Delayed motor skills development
• Cognitive impairment

Genetics

Pelizaeus–Merzbacher disease is caused by mutations in the PLP1 gene located on the X chromosome. This gene is responsible for producing proteolipid protein 1, a critical component of myelin. PMD is inherited in an X-linked recessive pattern, meaning that males are more frequently affected, while females are typically carriers.

Diagnosis

Diagnosis of PMD involves a combination of clinical evaluation, magnetic resonance imaging (MRI) to detect abnormalities in the brain's white matter, and genetic testing to identify mutations in the PLP1 gene.

Treatment

There is currently no cure for Pelizaeus–Merzbacher disease. Treatment focuses on managing symptoms and may include:

• Physical therapy to improve motor skills and muscle strength
• Occupational therapy to assist with daily activities
• Speech therapy to address communication difficulties
• Medications to manage spasticity and other symptoms

Prognosis

The prognosis for individuals with PMD varies depending on the type and severity of the disease. While some individuals may have a relatively stable course, others may experience significant deterioration in motor and cognitive functions.

Related Pages

• Leukodystrophy
• Myelin
• X-linked recessive inheritance
• PLP1 gene
• Nystagmus
• Hypotonia
• Ataxia
• Spasticity