Neuronal ceroid lipofuscinosis: What are the roles of electron microscopy, DNA, and enzyme analysis in diagnosis?

The neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal-storage disorders that occur primarily in children and rarely in adults. The childhood forms (infantile, late infantile, and juvenile NCLs) are inherited in an autosomal-recessive manner whereas adult NCL is reported to have an autosomal-dominant as well as an autosomal-recessive form. Clinical manifestations include progressive mental and motor degeneration, visual loss (childhood forms), seizures, and early death. The various forms of NCL are distinguished by age of onset, electron microscopy (EM), enzyme analysis, and gene involvement. Before the discovery of gene and protein defects responsible for NCL, identification of the pattern of characteristic inclusions by EM was the primary means of diagnosis before autopsy. Because NCL is a genetically and biochemically diverse disease, EM is still a valuable screening tool. Nevertheless, EM may not be the best first approach due to the invasive nature and cost. Current testing for enzyme deficiencies of palmitoyl-protein thioesterase 1 (PPT1) and tripeptidyl-peptidase 1 (TPPI) can be an effective and less invasive approach for some forms of NCL. This paper offers a review of the four forms of NCL, as well as a discussion of the role of EM and enzyme analysis in the diagnosis of NCL.