Neuronal ceroid lipofuscinosis (NCL) is a collection of distinct lysosomal storage diseases that, although rare, represents the most common progressive neurodegenerative childhood disease.
1–4 Currently, classification of NCL is based on specific genes (
CLN, ceroid lipofuscinosis, neuronal) and mutations involved, and the age at clinical manifestation.
5 Each
CLN gene is distinctly numbered to designate a respective subtype, of which there are currently 14 known genes affected.
6 The most common subtype is associated with mutations in
CLN2, also previously called Jansky–Bielschowsky disease or CLN2 disease.
7 CLN2 encodes for tripeptidyl peptidase 1 (TPP1), a lysosomal hydrolase that removes three amino acids from the
N-terminus of small polypeptides.
8,9 As a result, mutations in
CLN2 lead to the accumulation of curvilinear profiles in lysosomal residual bodies throughout the body, to which the central nervous system (CNS) and retina seem to be particular sensitive.
10 Patients often present between 2 and 4 years of age with delayed acquisition or deterioration of speech, motor decline, seizures, and ataxia, with a more pronounced and rapidly progressive deterioration of motor function, language, vision, and swallowing after age 3. The disease typically leads to premature death by early adolescence, although naturally the timing and course depends on the specific mutation.
11–14