Neuronal ceroid lipofuscinosis type 2 (NCL2) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the TPP1 gene, resulting in a reduction or complete loss of activity of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1).

This retrospective study provides the first systematic description of NCL2 in the Russian Federation. It includes an analysis of clinical manifestations, as well as biochemical and molecular genetic results from 50 patients with NCL2. The study characterizes the progression of phenotype development and identifies the onset and primary clinical symptoms.

The diagnosis of NCL2 was confirmed using biochemical and molecular genetic methods. In recent years, next-generation sequencing (NGS) has played a leading role among these techniques. During the study, nine different pathogenic variants in the TPP1 gene (NM_000391.3) were identified, including one variant not previously reported in the literature. A high frequency of the c.622C>T variant (75% of all mutant alleles) and the c.89+5G>C variant (14% of all mutant alleles) was observed.

A significant delay in diagnosis was identified, highlighting the need to develop diagnostic programs for the early detection of NCL2, especially in light of emerging pathogenetic therapies.

A separate section of the study is dedicated to analyzing the first domestic experience with enzyme replacement therapy (ERT) using cerliponase alfa. The findings indicate that early initiation of ERT can slow the progression of neurological symptoms, and the treatment’s effectiveness depends on how soon therapy begins.