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The latest on leukodystrophies
Raphael Schiffmann1, Marjo S van der Knaap
1Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Current Opinion in Neurology
|March 17, 2004
Summary
Genetic defects in eukaryotic initiation factor 2B (eIF2B) cause vanishing white-matter disease. Advances reveal a spectrum of eIF2B-related disorders and new leukodystrophy syndromes, impacting white matter health.
Area of Science:
- Neurogenetics
- White Matter Disorders
- Leukodystrophy
Background:
- Genetic disorders of white matter are increasingly understood.
- Advances in molecular genetics have identified novel causative genes and pathways.
Purpose of the Study:
- To review recent advances in the understanding of genetic white matter disorders.
- To highlight the role of eukaryotic initiation factor 2B (eIF2B) in leukodystrophy.
- To describe newly recognized clinical and imaging syndromes.
Main Methods:
- Literature review of recent findings in genetic white matter disorders.
- Focus on eIF2B-related disorders and their clinical spectrum.
- Discussion of adrenoleukodystrophy and myelin protein-related disorders.
Main Results:
- Mutations in eIF2B genes cause vanishing white-matter disease/childhood ataxia with central hypomyelination syndrome.
- eIF2B disorders present a spectrum from severe infantile encephalopathy to adult-onset cognitive decline.
- New syndromes include hypomyelination with basal ganglia/cerebellar atrophy and leukoencephalopathy with brain-stem/spinal cord involvement and elevated lactate.
- Mitochondrial fat-oxidation defects may contribute to adrenoleukodystrophy pathogenesis.
- Mutant myelin proteins can cause dysmyelination and axonal damage.
Conclusions:
- eIF2B is a significant cause of a common leukodystrophy syndrome with a wide clinical range.
- Two novel leukodystrophy syndromes, HABC and LBSL, are described.
- Updates on adrenoleukodystrophy and myelin protein disorders are provided.
- The identification of genetic defects causing primary white matter disorders is accelerating.