Neuronal ceroid lipofuscinosis type 2: An Australian case series

J Paediatr Child Health 2020 Aug;56(8):1210-1218. doi: 10.1111/jpc.14890. Epub 2020 Apr 24.

PMID: 32329550

Alexandra M Johnson, Simone Mandelstam, Ian Andrews

Highlights: This article aims to highlight typical clinical and radiological features that may prompt diagnosis of CLN2 disease in early disease stages.

Abstract

Aim: CLN2 disease (late infantile neuronal ceroid lipofuscinosis type 2) is a rare neurodegenerative disorder that begins with seizures and loss of motor and language skills in children aged 2-4 years and progresses to blindness and death in late childhood. The initial symptoms are similar to those of a number of typical epilepsies. The goal of this study is to identify common clinical and radiological features that can help the diagnosis of CLN2 disease in early stages.

Methods: We describe the clinical characteristics, disease progression, neuroimaging, electroencephalogram, biochemical, and genetic results of 13 Australian patients with CLN2 disease. On ten cases, expert neuroradiological magnetic resonance imaging (MRI) analysis was performed retrospectively.

Results: Twelve patients presented with seizures, with initial seizures being focal (n = 4), generalized tonic-clonic (n = 3), absence (n = 3) and febrile (n = 2). Before the beginning of seizures, 11 patients (85%) had a language delay. On a centralized MRI evaluation, all patients had cerebellar or cerebral atrophy, as well as anomalies in the brainstem, ventricles, corpus callosum, and hippocampi.

Conclusions: Early language delay with the onset of seizures at 2-4 years of age is the hallmark of CLN2 disease. Early mild atrophy in the cerebellum or posterior cortical regions on MRI should prompt CLN2 disease testing so that enzyme replacement therapy can be started sooner.

Keywords: cerebellar atrophy, cerebral atrophy, ceroid lipofuscinosis type 2 disease, epilepsy, language delay, magnetic resonance imaging