[Clinical features of 13 children with neuronal ceroid lipofuscinosis type 2]

Clinical data were retrospectively collected from 13 children with type 2 neuronal ceroid lipofuscinosis (CLN2) who underwent genetic testing for definitive diagnosis and were followed up at the Chinese PLA General Hospital from January 2018 to December 2023. The clinical features, disease progression, and prognosis were analyzed. The age at onset was [M(Q₁, Q₃)] 3.7 (3.2, 4.5) years, including 7 males and 6 females. The follow-up was conducted once every 3 months during the first 2 years after diagnosis, and once every 6 months starting from the 3rd year, with the last follow-up until December 2025. All patients presented with epilepsy as the initial manifestation, of whom 8 patients had myoclonic seizures. Psychomotor regression occurred in 10 patients shortly after seizure onset. Tripeptidyl peptidase 1 (TPP1) activity was below the normal reference range in all patients, and all harbored biallelic pathogenic or likely pathogenic variants in the TPP1 gene. Brain magnetic resonance imaging revealed cerebellar atrophy in all cases, and electroencephalography demonstrated generalized abnormalities in all patients. Disease progression exhibited relatively distinct stage-wise features. Within>1-2 years of onset, eleven patients developed ataxia and 10 experienced language regression. Within>2-3 years, ten patients had lost independent ambulation and 9 had lost language function. Within>3-5 years, all patients lost motor and language abilities, and 10 developed severe dysphagia. Five patients died during follow-up. In conclusion, CLN2 typically presents in early childhood with epilepsy as the predominant initial manifestation, followed by progressive neurofunctional decline and cerebellar atrophy. Markedly reduced TPP1 activity together with pathogenic TPP1 variants supports the diagnosis.