Update on leukodystrophies

Abstract

Leukodystrophies, heritable white matter disorders, have long presented significant diagnostic and therapeutic challenges to the practicing neurologist. Recent advances, however, have identified many of the unclassified leukodystrophies, and work in understanding the underlying pathophysiology of these diverse disorders has progressed. Several hypomyelination disorders have been identified, Aicardi–Goutières syndrome-associated genes have been found and autosomal-dominant leukodystrophy has been established as a genetically distinct disorder. In addition, unifying mechanisms in certain leukodystrophies have been found, including an abnormal endoplasmic reticulum stress response and astrocytic dysfunction. Finally, novel diagnostic approaches have established techniques for rapid identification of affected patients. This review provides an update of these changes and discusses the likely impact they will have on the evaluation and management of leukodystrophies.

Keywords: :

• astrocytes
• endoplasmic reticulum stress
• hypomyelination
• leukodystrophy
• myelin
• newborn screening
• white matter disorders

Financial disclosure

The authors have no relevant financial interests including employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties related to this manuscript.