Abstract | PURPOSE OF REVIEW: Important advances in our understanding of genetic disorders of the white matter have been made and are discussed here. RECENT FINDINGS: It has recently been discovered that mutations in the genes encoding the five subunits of eukaryocytic initiation factor 2B ( eIF2B) are the cause of vanishing white-matter disease/childhood ataxia with central hypomyelination syndrome. The extension of the clinical features of the eIF2B-related disorders to encompass both infant- and adult-onset disorders is discussed. New clinico-imaging syndromes such as hypomyelination with atrophy of the basal ganglia and cerebellum and leukoencephalopathy with brain-stem and spinal cord involvement and elevated white-matter lactate are described. Recent findings include evidence that mitochondrial fat-oxidation abnormalities may be important in the pathogenesis of adrenoleukodystrophy, and that a mutant myelin protein can cause maldistribution of other myelin proteins, causing dysmyelination, axonal damage, or both. SUMMARY: This review focuses on advances in the understanding of the role of eIF2B as a cause of a common leukodystrophy syndrome. eIF2B-related disorders have a clinical spectrum ranging from a severe, rapidly progressive congenital or early infantile encephalopathy to a slowly progressive cognitive and motor deterioration often associated with premature ovarian failure. Two newly recognized leukodystrophy syndromes are described: hypomyelination with atrophy of the basal ganglia and cerebellum, and leukoencephalopathy with brain-stem and spinal cord involvement and elevated white-matter lactate. An update is also given for adrenoleukodystrophy and myelin-protein-related disorders. This update demonstrates that an increasing number of genetic defects are being identified that may cause primary white-matter disorders.
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Authors | Raphael Schiffmann, Marjo S van der Knaap |
Journal | Current opinion in neurology
(Curr Opin Neurol)
Vol. 17
Issue 2
Pg. 187-92
(Apr 2004)
ISSN: 1350-7540 [Print] England |
PMID | 15021247
(Publication Type: Journal Article, Review)
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Chemical References |
- Eukaryotic Initiation Factor-2B
- Myelin Proteins
- Proteolipids
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Topics |
- Adrenoleukodystrophy
(diagnosis, genetics, pathology, physiopathology)
- Adult
- Atrophy
- Brain
(pathology, physiopathology)
- Child
- DNA Mutational Analysis
- Diagnosis, Differential
- Energy Metabolism
(genetics, physiology)
- Eukaryotic Initiation Factor-2B
(genetics)
- Hereditary Central Nervous System Demyelinating Diseases
(diagnosis, genetics, physiopathology)
- Humans
- Infant
- Myelin Proteins
(genetics)
- Nerve Fibers, Myelinated
(pathology)
- Proteolipids
(metabolism)
- Sphingolipidoses
(diagnosis, genetics, pathology, physiopathology)
- Spinal Cord
(pathology, physiopathology)
- Syndrome
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