10 Year Analysis of The Largest Cln2 Disease Regional Cohort In United Kingdom

Objectives: CLN2 disease (late-infantile neuronal ceroid lipofuscinosis) causes progressive neurological decline, refractory seizures, visual decline, and is fatal without treatment. We present 10 year data of diagnosing and managing this disorder in our region in the advent of intraventricular cerliponase alfa (enzyme replacement therapy; ERT). Methods: Case notes of all CLN2 patients diagnosed in the region over the past 10 years (2013-2023) were reviewed retrospectively. We analysed their presentation and evolution of symptoms including mobility, speech and language, seizure control and visual progress. Results: 22 cases were diagnosed over the study period. 32% (n=7) were diagnosed between July 2022 and July 2023, indicating an increased awareness of CLN2. All patients presented with speech delay and epilepsy. 2/21 were ineligible for ERT due to advanced disease stage and 2/21 with an attenuated form of the condition discontinued ERT within 12 months of commencing treatment. 17/21 remain on fortnightly ERT. Pre symptomatic or early symptomatic patients appeared to benefit the most from ERT, with some maintaining independent ambulation, speech and swallow. Seizures refractory to treatment were seldom seen in the cohort treated with ERT in comparison to our untreated cohort. Conclusion: Our data highlights the importance of early diagnosis of CLN2 and we strongly recommend that all children presenting with speech delay and epilepsy are tested urgently to facilitate early treatment.