Children with CLN2 disease

Pathophysiology

Neurodegeneration in children with CLN2 disease is associated with deficiency of the TPP1 enzyme1,2

Mutations in the CLN2/TPP1 gene
Mutations in the CLN2/TPP1 gene result in deficient activity of the tripeptidyl-peptidase 1 (TPP1) enzyme. TPP1 is a protease that cleaves N-terminal tripeptides from substrates in lysosomes.3-5
Accumulation of lysosomal autofluorescent lipopigment storage material
The absence or reduced activity of the TPP1 enzyme is associated with an accumulation of lysosomal autofluorescent lipopigment storage material.2,4
Cell dysfunction, death, and atrophy
Over time, cell dysfunction, cell death and atrophy occur.3,6
Continuous accumulation in lysosomes and progression of devastating symptoms are seen throughout the course of CLN2 disease

References: 1. Schulz A et al. NCL diseases — clinical perspectives. Biochim Biophys Acta 2013;1832:1801–1806. 2. Chang M et al. CLN2. In: Mole S, Williams R, and Goebel H, eds. The neuronal ceroid lipofuscinoses (Batten Disease). 2nd ed. Oxford, United Kingdom:Oxford University Press; 2011:80–109. 3. Mole SE, Williams RE. Neuronal ceroid-lipofuscinoses. In: Pagon RA, Adam MP, Ardinger HH, et al., eds. GeneReview® [internet]. Seattle, WA: University of Washington;1993–2016. 4. Mole SE et al. Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. Neurogenetics 2005;6:107–126. 5. Fietz M et al. Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis. Mol Genet Metab. 2016;119:160–167. 6. Haltia M. The neuronal ceroid-lipofuscinoses: From past to present. Biochim Biophys Acta 2006;1762:850–856.