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Pelizaeus-Merzbacher disease
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Pelizaeus-Merzbacher disease

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Contributors: Jennifer Vermilion MD, Jamie Adams MD, Richard L. Barbano MD, PhD
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Synopsis

Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive leukodystrophy caused by mutations in the proteolipid protein 1 gene (PLP1) that lead to abnormal myelination in the central nervous system. It is rare, with a prevalence of 1:200 000 to 1:500 000 in the United States.

There are 3 main forms of PMD: classic, connatal, and transitional. In classic PMD, symptom onset typically occurs in infancy. Initial symptoms include pendular nystagmus, head tremor, and hypotonia. As the disease progresses, children develop spastic quadriparesis, ataxia, abnormal movements (such as dystonia, chorea, and athetosis), and cognitive impairment. Most children learn to walk with assistive devices but often lose this skill as the disease progresses. Language may develop or may be limited depending on the severity of disease. Individuals with classic PMD typically survive until late adolescence or young adulthood.

Connatal PMD is the most severe form, presenting with nystagmus at birth, respiratory distress, stridor, and significant neonatal hypotonia. Seizures may be present as well. These children never learn to walk or talk. Death occurs between infancy and the 3rd decade of life.

Transitional PMD combines features of both classic and connatal PMD.

In addition to different forms of PMD, PLP1 mutations can lead to other neurologic disorders, including a spastic paraplegia (SPG2). SPG2 is characterized by spastic gait and autonomic dysfunction. These individuals have preserved cognition.

For more information, see OMIM.

Codes

ICD10CM:
E75.29 – Other sphingolipidosis

SNOMEDCT:
64855000 – Pelizaeus-Merzbacher disease

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

  • Cerebral palsy – This is a static process, unlike PMD.
  • PMD-like disease 1 – Congenital disorder of hypomyelination secondary to GJC2 mutations, autosomal recessive inheritance.
  • Other leukodystrophies – Nystagmus is atypical in these disorders (eg, metachromatic leukodystrophy, Krabbe disease, adrenoleukodystrophy, Canavan disease, Alexander disease).
  • Childhood ataxia with central nervous system hypomyelination / vanishing white matter disease
  • Congenital muscular dystrophy with merosin deficiency
  • Salla disease

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Last Reviewed: 02/19/2019
Last Updated: 02/19/2019
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Pelizaeus-Merzbacher disease
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Pelizaeus-Merzbacher disease (Connatal) : Seizures, Hypotonia, Nystagmus, Present at birth, Spasticity, Dysphagia, Dyspnea, Stridor
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