A 41 year-old Japanese male diagnosed with megalencephalic leukoencephalopathy (MLC) with subcortical cysts (van der Knaap disease), presenting at 1 year of age with macrocephaly, slowly progressing after 5 years, seizures beginning at 11 years, completely bed ridden at 18 years, and with long survival, is reported from Tokyo Metropolitan Higashiyamato Medical Center for the Severely Disabled, Japan. His motor function had severely deteriorated and his cognitive function was at a 2 year level. MRI revealed marked cerebral atrophy, ventricular enlargement, and large cysts in frontoparietal and anterior temporal areas. A homozygous missense mutation was detected in the MLC1 gene. [1]
COMMENT. Van der Knaap and colleagues described an infantile onset leukoencephalopathy with swelling and a discrepantly mild clinical course in 8 children in 1995. Mutations of MLC1 gene were identified as a cause of the leukoencephalopathy with subcortical cysts in 2001 (Leegwater et al). The changes in size of basal ganglia and diffuse white matter abnormalities that characterize Canavan and Alexander diseases are not evident in MLC.