The combined application of recently developed techniques for genetic and biochemical analysis, neuroimaging and the ability to create animal models has led to remarkable advances in the field of leukodystrophy research. The present review focuses on recent developments in X-linked adrenoleukodystrophy, Alexanders disease, Canavans disease, metachromatic leukodystrophy, globoid cell leukodystrophy (Krabbes disease) and Pelizaeus-Merzbacher disease, and briefly discusses new data on six other rare inherited leukodystrophies. Of the leukodystrophies, 12 can now be diagnosed precisely using noninvasive techniques, and the molecular defect has been identified in nine of these. Disease incidence can be reduced through genetic counselling. Presymptomatic diagnosis provides an opportunity for therapeutic intervention. Study of animal models facilitates elucidation of pathogenic mechanisms and identifies pathways that could be targeted by future therapies.
aBrain Research Institute, Division of Neuroimmunology, University of Vienna, Vienna, Austria, and bKennedy Krieger Institute, Baltimore, Maryland, USA
Correspondence to Johannes Berger, PhD, Brain Research Institute, Division of Neuroimmunology, University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria. Tel: +43 1 4277 62812; fax: +43 1 4277 9628; e-mail: email@example.com
Abbreviations BMT: bone marrow transplantation CNS: central nervous system GFAP: glial fibrillary acidic protein GLD: globoid cell leukodystrophy MLD: metachromatic leukodystrophy MRI: magnetic resonance imaging NAA: N-acetyl aspartate PLP: proteolipid protein PMD: Pelizaeus-Merzbacher disease SPG2: spastic paraplegia type 2 VLCFA: very long-chain fatty acid X-ALD: X-linked adrenoleukodystrophy