Diagnosis of neuronal ceroid lipofuscinosis: mutation detection strategies.

The neuronal ceroid lipofuscinoses (NCL) are a group of rare genetically inherited neurodegenerative disorders in children. These diseases are classified by age of onset (congenital, infantile, late-infantile, juvenile and adult-onset) and by the gene bearing mutations (CLN10/CTSD, CLN1/PPT1, CLN2/TPP1, CLN3, CLN5, CLN6, CLN7/MFSD8 and CLN8). Enzyme activity assays are helpful in identifying several of these disorders; however confirmation of the mutation in the gene causing these diseases is vital for definitive diagnosis. There exists considerable heterogeneity in the NCLs as a whole and within each type of NCL both in phenotype (disease manifestation and progression) and genotype (type of mutation), which complicates NCL diagnosis. In order to streamline the diagnostic process, the age of symptom onset, geography and/or ethnicity, and enzyme activity may be considered together. However, these ultimately serve to guide targeting the correct route to genetic confirmation of an NCL through mutational analysis. Herein, an effective protocol to diagnose NCLs using these criteria is presented.