Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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April 4, 2011
Pelizaeus-Merzbacher Disease (PMD)
- Pelizaeus-Merzbacher Disease is a rare leukodystrophy which results from abnormality of PLP1 gene on chromosome Xq22 coding for proteolipid protein 1 and a smaller protein (DM20), two primary components of myelin.
- PMD has a "classic" form as well a more severe form known as "connatal" form. The classic form shows X-linked recessive inheritance, and patients usually present in first year of life with nystagmus, delayed motor and cognitive milestones, and ataxia. The connatal form shows either autosomal or X-linked recessive inheritance and usually presents at birth or in early infancy. In addition to nystagmus and extrapyramidal hyperkinesia, patients have spasticity, optic atrophy and seizure. Patients with classic form usually live until late adolescence or early adulthood, but in connatal form, death usually occurs in early childhood.
- There is a group of patients with similar clinical presentation but normal appearing white matter at biopsy and on MRI and no evidence of mutation of PLP1 gene. These group of patients are considered to have Pelizaeus-Merzbacher-like disease.
- Key Diagnostic Features: PMD appears as low signal intensity white matter on CT scan, and on MRI, it appears as lack of myelination as opposed to myelin destruction. Depending on the severity of the disease, there might be some myelination within internal capsules, optic radiations and proximal corona radiata. In severe cases, there could be complete absence of low T2 signal intensity within the white matter. The cerebellum may be markedly atrophic. MRI cannot differentiate classic form from connatal form although it has been noted that some degree of myelination is seen in patients with the classic form, whereas no evidence of myelin is seen in connatal form.
- MR spectroscopy findings in PMD are controversial likely because of different mutations of the PLP gene. Molecular diagnostic testing is the definitive method to diagnose PMD by detecting mutations of the PLP1 gene.
- Treatment: No specific treatment for PMD is available and medical care is mostly limited to supportive care such as physical therapy, anti-spasticity agents, and orthotics.
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