Leukodystrophy, Hypomyelinating, 2

Alternative Names

  • HLD2
  • Pelizaeus-Merzbacher-Like Disease, 1
  • PMLD1
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Metabolic disorders

OMIM Number


Mode of Inheritance

Autosomal recessive

Gene Map Locus



Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating leukoencephalopathy disorder with a genetically heterogeneous pattern.  It is virtually identical to Pelizaeus-Merzbacher disease (PMD) but without a mutation in the PLP1 gene that causes PMD.  The prevalence is unknown, affecting males and females with equal frequency.  PMLD is characterized by early-onset nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity. 

There is no standard treatment for individuals with Pelizaeus-Merzbacher like disease.  Treatment is based upon specific symptoms present and supportive care.

Molecular Genetics

PMLD1 is inherited as an autosomal recessive trait.  To date, 25 different mutations in the GJA12/GJC2 gene, which encodes the gap junction protein 12, have been identified in patients with autosomal recessive Pelizaeus¬-Merzbacher-like disease.  This protein plays a key role in central myelination and is involved in peripheral myelination.  Missense, nonsense, frameshift, and indel mutations have been reported.  Also a mutation in the promoter of GJC2 was reported to cause PMLD1.

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

Bugiani et al. (2006) described the clinical and neuroimaging features of 13 patients with Pelizaeus-Merzbacher-Like Disease (PMLD) from 10 families.  Eight of these patients (patients 5 to 12) were from a multi-consanguineous Saudi family.  All patients presented in the neonatal period with rotatory or pendular nystagmus.  Around the age of 6-months they had moderate to severe psychomotor delay, followed by cerebellar ataxia, intention tremor, and slurred, dysarthric speech, evolving into spastic tetraparesis.  Patients 9 to 12 had more severe symptoms; they were unable to walk, and their cerebellar tremor was severely disabling.  All patients were alive, ranging from age 4 to 23-years.  Ophthalmologic examination showed pale optic disc, and frank optic atrophy in patients 5 and 6.  All patients had normal motor and sensory nerve conduction velocities.  MRI revealed a remarkable, diffuse myelin deficiency in all patients, except in patient 5, who displayed a much lesser degree of signal changes.  A 22-bp duplication mutation in the GJC2 gene was found in the eight PMLD patients.

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