Review Note

Last Update: 04/01/2024 02:31 AM

Current Deck: Neurology::RITE

Published

Pelizaeus-Merzbacher disease:

inheritance? {{c1::x-linked recessive}}
mutation? {{c2::mutations in proteolipid protein 1 (PLP1), a major myelin protein}}
pathophys? {{c3::hypomyelination (a leukodystrophy)}}

Hypomyelinating leukodystrophy inherited in an X-linked recessive fashion.
PLP1 on chromosome Xq22.2, and the mutation leads to abnormal synthesis of proteolipid protein 1
Mutations in this same gene also account for one form of hereditary spastic paraplegia.
The onset of clinical manifestations is in the first few months of life, with intermittent nodding movements of the head, pendular nystagmus, and other abnormal eye movements. Ataxia, chorea, athetosis, dystonia, spasticity, and laryngeal stridor also occur, and psychomotor development arrests with subsequent regression.
Late manifestations include seizures and optic atrophy. Patients with later onset may have slower progression, and some patients survive into adulthood.
MRI demonstrates diffuse hypomyelination characterized by T2 hyperintensity and loss of white matter with relative thinning of the corpus callosum. Pathologically, there is a noninflammatory demyelination sparing the U fibers and islands of white matter. This patchy involvement gives it a “tigroid” appearance on MRI.
Peripheral myelin is spared and, therefore, peripheral nerves are not involved.
Genetic testing is available for diagnosis, and there is no specific treatment

Hereditary Disorders of Myelin Metabolism

Adrenoleukodystrophy
Metachromatic leukodystrophy
Krabbe disease
Alexander disease
Canavan-van Bogaert-Bertrand disease Pelizaeus-Merzbacher disease Phenylketonuria