Introduction: 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.
Areas covered: 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. We also describe common diagnostic challenges and some potential misdiagnoses that may occur during differential diagnosis.
Expert opinion: 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.
Bibliographical noteFunding Information:
P Striano developed this research within the framework of the DINOGMI Department of Excellence of MIUR 2018–2022 (Legge 232 del 2016). This manuscript was developed after discussions at a meeting of experts organized and supported by BioMarin Europe Ltd. Writing support was provided by Emma Conran, Porterhouse Medical, Reading, UK, and funded by BioMarin Europe Ltd.
All authors received an honorarium from BioMarin Europe Ltd for their contributions to an expert meeting at which it was agreed that this manuscript should be developed. In addition, H Huidekoper reports institutional reimbursement from BioMarin Europe Ltd, outside of the submitted work. M Mazurkiewicz-Bełdzińska reports personal fees from Biogen; personal fees from Roche; personal fees from BioMarin Europe Ltd; and personal fees from Novartis, outside of the submitted work. C Mühlhausen reports personal fees from PTC Therapeutics Germany GmbH, outside of the submitted work. I Prpić reports non-financial support from Dravet Syndrome Association Croatia; grants, personal fees and non-financial support from BioMarin Europe Ltd; non-financial support from Merck; non-financial support from Belupo d.d.; personal fees and non-financial support from Makpharm d.o.o.; personal fees and non-financial support from Pliva d.o.o.; non-financial support from Academy for Child Neurodevelopment; personal fees from Medis d.o.o.; non-financial support from the organizer of ‘New Challenges in Paediatrics’ Symposium, Croatia, March 2020; and personal fees and non-financial support from BioMarin Pharmaceutical Inc., outside of the submitted work. P Striano reports personal fees from Zogenix; personal fees from GW Pharmaceuticals; personal fees from Enecta BV; and personal fees from Proveca during the conduct of the study. S Auvin reports personal fees and non-financial support from BioMarin, outside of the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.