The neuronal ceroid-lipofuscinoses (NCLs) collectively constitute the most common group of neurodegenerative diseases in childhood and usually show an autosomal recessive mode of inheritance. Despite varying ages of onset and clinical course characterized in most instances by progressive mental and motor deterioration, blindness, epileptic seizures, and premature death, all forms of NCL show unifying histopathological features. There is accumulation of autofluorescent, periodic acid-Schiff-, and Sudan black B-positive granules that are resistant to lipid solvents in the cytoplasm of most nerve cells and. to a lesser degree, of many other cell types. The storage process is associated with progressive and selective neuronal loss and gliosis with secondary white matter lesions. The ultrastructure of the storage deposits varies between different forms of NCL and, along with the age of onset, has provided the basis for the traditional classification of NCLs. Recent molecular genetic findings have established that defects in at least 7 different genes underlie the various forms of NCL. The purpose of this paper is to provide an overview of the NCLs, review recent molecular genetic and biochemical findings, and discuss their impact on our views on the classification and pathogenesis of these devastating brain disorders.
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