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Disease Profile

Pelizaeus-Merzbacher-like disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

E75.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

PMLD

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 280270

Definition
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).

Epidemiology
Prevalence is unknown.

Clinical description
It is characterized by early-onset nystagmus, delayed motor milestones, progressive spasticity, ataxia, and diffuse leukodystrophy on MRI.

Etiology
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.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Ataxia
0001251
Autosomal recessive inheritance
0000007
Babinski sign
0003487
Cerebral atrophy
Degeneration of cerebrum
0002059
Cerebral hypomyelination
0006808
Choreoathetosis
0001266
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Decreased motor nerve conduction velocity
0003431
Demyelinating motor neuropathy
0007220
Dysarthria
Difficulty articulating speech
0001260
Dystonia
0001332
Facial palsy
Bell's palsy
0010628
Global developmental delay
0001263
Head titubation
0002599
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Intention tremor
0002080
Leukodystrophy
0002415
Motor delay
0001270
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Optic atrophy
0000648
Poor speech
0002465
Progressive spasticity
0002191
Rigidity
Muscle rigidity
0002063
Rotary nystagmus
0001583
Seizure
0001250
Sensory axonal neuropathy
0003390
Spastic paraparesis
0002313

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Providing General Support

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    In-Depth Information

    • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
    • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
    • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
    • PubMed is a searchable database of medical literature and lists journal articles that discuss Pelizaeus-Merzbacher-like disease. Click on the link to view a sample search on this topic.