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Pelizaeus-Merzbacher like disease (PMLD) is an autosomal recessive leukodystrophy sharing identical clinical and radiological features as X-linked Pelizaeus-Merzbacher disease (PMD; see this term).
ORPHA:280270Classification level: Disorder
Prevalence is unknown.
It is characterized by early-onset nystagmus, delayed motor milestones, progressive spasticity, ataxia, and diffuse leukodystrophy on MRI.
One PMLD form is due to mutations in the GJC2 gene encoding the gap junction protein C2. There are very likely other PMLD forms that have not been defined but that are caused by mutations affecting other genes involved in myelination. Other syndromes have also been referred to as PMLD but their inclusion as PMLD has been debated because of their severity and of the evidence of neuronal, besides white matter, involvement on MRI. These syndromes include an autosomal recessive syndrome due to mutations in the HSPD1 gene, encoding the heat shock protein 1, that resembles severe PMD (nystagmus, developmental delay, spasticity, feeding and breathing problems, early-onset lethality) and that is associated with acquired microcephaly, as well as a syndrome due to mutations in the AIMP1 gene, encoding the aminoacyl tRNA synthetase complex-interacting multifunctional protein 1, and characterized by nystagmus, axial hypotonia, spastic paraparesis, severe developmental delay, kyphoscoliosis, microcephaly, intellectual deficit, and absence of speech. An X-linked syndrome, allelic to Allan-Herndon-Dudley syndrome (see this term), has also been referred to as a PMLD. This syndrome is characterized by neonatal hypotonia, nystagmus, progressive spastic paraplegia, ataxia and developmental delay, and is due to mutations in the SLC16A2 gene encoding the monocarboxylate transporter 8 involved in thyroid hormone transport. However, MRI findings are not as severe as those of PMD (diffuse hypomyelination), and tend to improve over time, making this more of a delayed myelination disorder that is probably secondary to a neuronal dysfunction related to impaired thyroid hormone transport.
- Clinical genetics review
- English (2018)