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.