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. 2021 Apr 21;16(1):185.
doi: 10.1186/s13023-021-01813-5.

Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients

Sara E Mole #  1 , Angela Schulz #  2 , Eben Badoe  3 , Samuel F Berkovic  4 , Emily C de Los Reyes  5 , Simon Dulz  2 , Paul Gissen  6   7 , Norberto Guelbert  8 , Charles M Lourenco  9 , Heather L Mason  10 , Jonathan W Mink  11 , Noreen Murphy  12 , Miriam Nickel  2 , Joffre E Olaya  13 , Maurizio Scarpa  14 , Ingrid E Scheffer  4   15 , Alessandro Simonati  16 , Nicola Specchio  17 , Ina Von Löbbecke  18 , Raymond Y Wang  13 , Ruth E Williams  19
Affiliations

Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients

Sara E Mole et al. Orphanet J Rare Dis. .

Abstract

Background: CLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2) is an ultra-rare, neurodegenerative lysosomal storage disease, caused by an enzyme deficiency of tripeptidyl peptidase 1 (TPP1). Lack of disease awareness and the non-specificity of presenting symptoms often leads to delayed diagnosis. These guidelines provide robust evidence-based, expert-agreed recommendations on the risks/benefits of disease-modifying treatments and the medical interventions used to manage this condition.

Methods: An expert mapping tool process was developed ranking multidisciplinary professionals, with knowledge of CLN2 disease, diagnostic or management experience of CLN2 disease, or family support professionals. Individuals were sequentially approached to identify two chairs, ensuring that the process was transparent and unbiased. A systematic literature review of published evidence using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance was independently and simultaneously conducted to develop key statements based upon the strength of the publications. Clinical care statements formed the basis of an international modified Delphi consensus determination process using the virtual meeting (Within3) online platform which requested experts to agree or disagree with any changes. Statements reaching the consensus mark became the guiding statements within this manuscript, which were subsequently assessed against the Appraisal of Guidelines for Research and Evaluation (AGREEII) criteria.

Results: Twenty-one international experts from 7 different specialities, including a patient advocate, were identified. Fifty-three guideline statements were developed covering 13 domains: General Description and Statements, Diagnostics, Clinical Recommendations and Management, Assessments, Interventions and Treatment, Additional Care Considerations, Social Care Considerations, Pain Management, Epilepsy / Seizures, Nutritional Care Interventions, Respiratory Health, Sleep and Rest, and End of Life Care. Consensus was reached after a single round of voting, with one exception which was revised, and agreed by 100% of the SC and achieved 80% consensus in the second voting round. The overall AGREE II assessment score obtained for the development of the guidelines was 5.7 (where 1 represents the lowest quality, and 7 represents the highest quality).

Conclusion: This program provides robust evidence- and consensus-driven guidelines that can be used by all healthcare professionals involved in the management of patients with CLN2 disease and other neurodegenerative disorders. This addresses the clinical need to complement other information available.

Keywords: Batten; CLN2; Expert mapping; Guideline development program; Key Opinion Leader; Modified-Delphi; Neurodegenerative disorder.

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Conflict of interest statement

Professor Sara Mole: Declares personal fees from Care Beyond Diagnosis for professional advice; Grants from BioMarin outside the submitted work. Dr Angela Schulz: Declares personal fees from Care Beyond Diagnosis for professional advice; Declares a grant and personal fees received from BioMarin for honoraria and advisory board attendance. Prof. E. Badoe: Declares personal fees from Care Beyond Diagnosis for professional advice. Dr S. Berkovic: Declares personal fees from Care Beyond Diagnosis for professional advice. Dr. Emily de Los Reyes: Declares personal fees from Care Beyond Diagnosis for professional advice; Declares a grant and personal fees received from BioMarin for consultation services. Dr. Simon Dulz: Declares personal fees from Care Beyond Diagnosis for professional advice. Dr P. Gissen: Declares personal fees from Care Beyond Diagnosis for professional advice; Declares a grant and personal fees received from BioMarin, during the conduct of the study. Dr. N. Guelbert: Declares personal fees from Care Beyond Diagnosis for professional advice. Dr. C. Lourenco: Declares personal fees from Care Beyond Diagnosis for professional advice. Dr. Heather L. Mason: Declares personal fees from Care Beyond Diagnosis for professional medical writing services. Ms N. Murphy: Declares personal fees from Care Beyond Diagnosis for professional advice. Dr. J. W. Mink: Declares personal fees from Care Beyond Diagnosis for professional advice; Reports personal fees from Neurogene, Inc., personal fees from Amicus, Inc., grants from Beyond Batten Disease Foundation, grants from Abeona Inc., personal fees from Abide Therapeutics, personal fees from Censa Inc., personal fees from Cipla, Inc., personal fees from TEVA Inc., outside the submitted work. Dr M. Nickel: Declares personal fees from Care Beyond Diagnosis for professional advice. Dr. J. Olaya: Declares personal fees from Care Beyond Diagnosis for professional advice. Dr. M Scarpa: Declares personal fees from Care Beyond Diagnosis for professional advice. Prof. I. Scheffer: Declares personal fees from Care Beyond Diagnosis for professional advice; Declares receipt of grants from NHMRC, grants from NIH, during the conduct of the study; personal fees from GlaxoSmithKline, personal fees from Eisai, personal fees from Nutricia, personal fees from GW Pharmaceutical, personal fees from Xeonon, personal fees from BioCodex, personal fees from BioMarin, personal fees from UCB, outside the submitted work; In addition, Dr. Scheffer has a patent for SCN1A testing held by Bionomics Inc and licensed to various diagnostic companies; was a consultant to Bionomics and Athena diagnostics previously, and holds a patent Molecular diagnostic/theranostic target for benign familial infantile epilepsy (BFIE) [PRRT2] 2011904493 & 2012900190 and PCT/AU2012/001321Ðu8226• TECH ID:2012-009 with royalties paid. Dr. A. Simonati: Declares personal fees from Care Beyond Diagnosis for professional advice; Declares personal fees received from BioMarin, Neurogene Inc, UCB SA, for honoraria and advisory board attendance. Dr. N. Specchio: Declares personal fees from Care Beyond Diagnosis for professional advice; Declares receipt of a grant from BioMarin, outside of the submitted work. Dr. I. von Löbbecke: Declares personal fees from Care Beyond Diagnosis for professional advice; Declares receipt of personal fees from and BioMarin. Dr. R. Wang: Declares personal fees from Care Beyond Diagnosis for professional advice; Declares receipt of a grant, research funding, honoraria for advisory board attendance, and equity ownership from BioMarin and RegenxBio Inc. Dr Ruth E. Williams: Declares personal fees from Care Beyond Diagnosis for professional advice.

Figures

Fig. 1
Fig. 1
A palliative care framework for CLN2 disease management facilitates comprehensive care of patients and families. Figure taken from Williams et al. [25] Management strategies for CLN2 disease. http://dx.doi.org/10.1016/j.pediatrneurol.2017.01.034. Published by Elsevier Inc. an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
See this image and copyright information in PMC

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