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

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

PMID: 33882967

Sara E Mole, Angela Schulz, Eben Badoe, Samuel F Berkovic, Emily C de Los Reyes, Simon Dulz, Paul Gissen, Norberto Guelbert, Charles M Lourenco, Heather L Mason, Jonathan W Mink, Noreen Murphy, Miriam Nickel, Joffre E Olaya, Maurizio Scarpa, Ingrid E Scheffer, Alessandro Simonati, Nicola Specchio, Ina Von Löbbecke, Raymond Y Wang, Ruth E Williams

Summary: The guidelines in this study provide solid evidence-based and expert-agreed advice on the risks/benefits of disease-modifying treatments and medical procedures used for the management of patients with CLN2 disease and other neurodegenerative diseases.

Abstract

Background: CLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2) is an ultra-rare, neurodegenerative lysosomal storage disease, caused by tripeptidyl peptidase 1 (TPP1) enzyme deficiency. Delays in diagnosis are often caused by lack of disease awareness and the non-specificity of presenting symptoms. The guidelines in this study provide solid evidence-based and expert-agreed advice on the risks/benefits of disease-modifying treatments and medical procedures used to manage this disorder.

Methods: Multidisciplinary professionals with knowledge of CLN2 disease, diagnostic or management experience with CLN2 disease, or family support professionals were ranked using an expert mapping tool method. A systematic literature review of published evidence was performed separately and concurrently using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance to establish key statements based on the strength of the publications. Clinical care statements served as the foundation for an international adapted Delphi consensus determination process that used the virtual meeting (Within3) online platform to ask experts if they agreed or disagreed with any changes. The consensus statements became the guiding statements in this manuscript, which were then evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREEII) criteria.

Results: 21 international experts from 7 different specialities were identified, including a patient advocate. 53 guideline statements were established covering 13 topics: 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 Steering Committee (SC) and achieved 80% consensus in the second voting round. For the development of the guidelines, the overall AGREEII assessment score obtained was 5.7. (where 1 represents the lowest quality, and 7 represents the highest quality).

Conclusion: All healthcare professionals engaged in the management of patients with CLN2 disease and other neurodegenerative diseases will benefit from this program, which offers solid evidence-based and consensus-driven recommendations. This indicates the clinical need for the complement of other information currently available.