In 2 daughters of Iraqi first-cousin parents, Harbord et al. (1990) observed a progressive neurologic disorder characterized by megalencephaly, spasticity, ataxia, and seizures. Onset of manifestations occurred between ages 2 and 3. Computerized tomography scans showed diffuse hypodensity ... In 2 daughters of Iraqi first-cousin parents, Harbord et al. (1990) observed a progressive neurologic disorder characterized by megalencephaly, spasticity, ataxia, and seizures. Onset of manifestations occurred between ages 2 and 3. Computerized tomography scans showed diffuse hypodensity of the white matter, and brain biopsy in one showed dysmyelination without evidence of demyelination. The electroencephalogram showed posterior discharges and an unusual photoparoxysmal response; the findings of brainstem auditory evoked potentials were consistent with a white matter disorder. The combination of megalencephaly with diffuse white matter hypodensity on brain imaging is found in Alexander disease (203450), Canavan disease (271900), and GM1 gangliosidosis (230500). Brain biopsy showed no Rosenthal fibers typical of Alexander disease or spongy changes characteristic of Canavan disease. Furthermore, no deficiency of aspartoacylase or of beta-galactosidase was found to support the diagnosis of Canavan disease or GM1 gangliosidosis, respectively. Harbord et al. (1990) suggested that the disorder in the sisters was a previously undescribed condition.