Managing CLN2 disease: a treatable neurodegenerative condition among other treatable early childhood epilepsies

Abstract

Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare pediatric neurodegenerative condition, which is usually fatal by mid-adolescence. Seizures are one of the most common early symptoms of CLN2 disease, but patients often experience language deficits, movement disorders, and behavioral problems. Diagnosis of CLN2 disease is challenging (particularly when differentiating between early-onset developmental, metabolic, or epileptic syndromes), and diagnostic delays often overlap with rapid disease progression. An enzyme replacement therapy (cerliponase alfa) is now available, adding CLN2 disease to the list of potentially treatable disorders requiring a prompt diagnosis. Although advances in enzymatic activity testing and genetic testing have facilitated diagnoses of CLN2 disease, our review highlights the presenting symptoms that are vital in directing clinicians to perform appropriate tests or seek expert opinion. The authors also describe common diagnostic challenges and some potential misdiagnoses that may occur during differential diagnosis. An awareness of CLN2 disease as a potentially treatable disorder and increased understanding of the key presenting symptoms can support selection of appropriate tests and prompt diagnosis. The available enzyme replacement therapy heralds an even greater imperative for early diagnosis, and for clinicians to direct patients to appropriate diagnostic pathways.