Economical diagnosis of neuronal ceroid lipofuscinoses

The neuronal ceroid lipofuscinoses (NCL) are characterized by the combination of dementia, epilepsy, and retinopathy and by the intracellular storage of a material defined by its ultrastructural morphology. Presently ten different genetic forms of NCL are known, designated CLN1 through CLN10. Lysosomal enzyme deficiencies occur in CLN1, CLN2, and CLN10, deficient membrane proteins in other forms. Some NCL types manifest at a characteristic age. Suspecting an NCL is at hand by the typical combination of symptoms and the progressive nature of the condition, whereas arriving at a diagnosis may be difficult and require facilities not readily available. Our diagnostic strategy starts with the use of dried blood spots for the detection of deficient palmitoylprotein thioesterase (CLN1), deficient tripeptidyl peptidase (CLN2), and the presence of the most frequently encountered mutation (in ˜ 80%) in CLN3. These tests will identify the large majority of NCL cases. When results are negative, we encourage consultation between the local physician and our center. Depending on the clinical picture, molecular genetic analysis of genes for rare NCL types is initiated. Patients in whom known NCL mutations have been excluded and where ultrastructural studies demonstrate storage material are investigated scientifically. The combination of expert advice (http://ncl-net.com) and analysis of dried blood provides an efficient approach to diagnose NCL disorders.