Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis

Neuronal ceroid lipofuscinoses (NCLs) are a group of rare, inherited, neurodegenerative lysosomal storage disorders that affect children and adults. They are traditionally grouped together, based on shared clinical symptoms and pathological ground. To date, 13 autosomal recessive gene variants, as well as one autosomal dominant gene variant, of NCL have been described. These genes encode a variety of proteins, whose functions have not been fully defined; most are lysosomal enzymes, transmembrane proteins of the lysosome, or other organelles. Common symptoms of NCLs include the progressive loss of vision, mental and motor deterioration, epileptic seizures, premature death, and, in rare adult-onset cases, dementia. Depending on the mutation, these symptoms can vary, with respect to the severity and onset of symptoms by age. Currently, all forms of NCL are fatal, and no curative treatments are available. Herein, we provide an overview to summarize the current knowledge regarding the pathophysiology, genetics, and clinical manifestation of these conditions, as well as the approach to diagnosis.