Vacuolating megalencephalic leukoencephalopathy in 12 Israeli patients

Leukodystrophy with macrocephaly as the main features of infantile neurodeg enerative disease are characteristics of Canavan's disease, L-2-hydroxyglut aric aciduria, type I glutaric aciduria, and Alexander's disease. Also occa sionally described are occidental congenital muscular dystrophy, G(M2)-gang liosidosis, metachromatic leukodystrophy, Krabbe's disease, and mucopolysac charidosis. Since 1995, over 60 patients with a new syndrome, vacuolating m egalencephalic leukoencephalopathy, have been described. The syndrome is ch aracterized by macrocephaly. a slowly progressive clinical course of ataxia , spastic paraparesis, and seizure disorder with relatively spared cognitio n. Unlike other leukodystrophies with macrocephaly (except Alexander's dise ase), no metabolic marker has been found. We describe a similar group of 12 patients from two different Jewish ethnic origins in whom consanguinity is prominent. These patients have neuroimaging features and magnetic resonanc e spectroscopy findings indicating that there is an initial increase in whi te-matter edema with subsequent cystic formation. Consistent with loss of t issue in these areas, brain metabolites are reduced. The familial incidence in this group of patients is suggestive of autosomal-recessive inheritance .