Unraveling neuronal ceroid lipofuscinosis type 2 (CLN2) disease: A tertiary center experience for determinants of diagnostic delay

Eur J Paediatr Neurol 2021 Jul;33:94-98. doi: 10.1016/j.ejpn.2021.05.015. Epub 2021 Jun 4.

PMID: 34119739

Didem Ardicli, Goknur Haliloglu, Rahsan Gocmen

Highlights: In this study, the majority of the patients presented with late-infantile onset seizures. Despite improved access to enzymatic and molecular testing, there is still a significant diagnostic delay.

Abstract

Objective: To assess the clinical phenotype, disease course, laboratory, and genetic characteristics of patients with CLN2 disease over a 20 year period with a focus on risk factors for diagnostic delay.

Methods: Thirty individuals (23 families) with CLN2 disease were examined in a tertiary referral center in Turkey between 1996 and 2019. Clinical characteristics, diagnostic pathway, disease course, genetic information, electrophysiological, and neuroimaging results were retrospectively examined. Patients diagnosed between 1996 and 2009, and 2010 to 2019, were divided into two groups, retrospectively: group 1 (G1) and group 2 (G2). These two groups of patients were also compared.

Results: The median age at the onset of symptoms was 36 months (20 months-7 years). Seizures were the most prevalent presenting symptom (70%), followed by language delay (43%), and psychomotor regression (27%). The median age at diagnosis was 5.2 years (1.6-11 years), with a median diagnostic delay of 27 months (1 month-7 years). G2 had a younger age at diagnosis (4.6 vs 7 years, p = 0.002) and a shorter duration to diagnosis (21 vs 39 months, p = 0.004). The median duration from the beginning of the first symptoms to death was 8.3 years (SE 1.0). Electroencephalograms (EEG) indicated abnormalities mostly in the posterior hemispheric areas, and 53 percent of the patients had a photoparoxysmal response to intermittent photic stimulation. The most prevalent radiological abnormalities were cerebellar (96%)/cerebral atrophy (83%) and white matter alterations (57%), respectively.

Conclusions: The majority of our patients presented with late-infantile onset seizures. Despite improved access to enzymatic and molecular testing, there is still a significant diagnostic delay.

Keywords: Diagnostic delay, Epilepsy, Language delay, Neuronal ceroid lipofuscinosis type 2, Photoparoxysmal response