PMID- 34000449 OWN - NLM STAT- MEDLINE DCOM- 20220202 LR - 20220202 IS - 1873-5150 (Electronic) IS - 0887-8994 (Linking) VI - 120 DP - 2021 Jul TI - Management of CLN1 Disease: International Clinical Consensus. PG - 38-51 LID - S0887-8994(21)00069-2 [pii] LID - 10.1016/j.pediatrneurol.2021.04.002 [doi] AB - BACKGROUND: CLN1 disease (neuronal ceroid lipofuscinosis type 1) is a rare, genetic, neurodegenerative lysosomal storage disorder caused by palmitoyl-protein thioesterase 1 (PPT1) enzyme deficiency. Clinical features include developmental delay, psychomotor regression, seizures, ataxia, movement disorders, visual impairment, and early death. In general, the later the age at symptom onset, the more protracted the disease course. We sought to evaluate current evidence and to develop expert practice consensus to support clinicians who have not previously encountered patients with this rare disease. METHODS: We searched the literature for guidelines and evidence to support clinical practice recommendations. We surveyed CLN1 disease experts and caregivers regarding their experiences and recommendations, and a meeting of experts was conducted to ascertain points of consensus and clinical practice differences. RESULTS: We found a limited evidence base for treatment and no clinical management guidelines specific to CLN1 disease. Fifteen CLN1 disease experts and 39 caregivers responded to the surveys, and 14 experts met to develop consensus-based recommendations. The resulting management recommendations are uniquely informed by family perspectives, due to the inclusion of caregiver and advocate perspectives. A family-centered approach is supported, and individualized, multidisciplinary care is emphasized in the recommendations. Ascertainment of the specific CLN1 disease phenotype (infantile-, late infantile-, juvenile-, or adult-onset) is of key importance in informing the anticipated clinical course, prognosis, and care needs. Goals and strategies should be periodically reevaluated and adapted to patients' current needs, with a primary aim of optimizing patient and family quality of life. CI - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Augustine, Erika F AU - Augustine EF AD - Department of Neurology and Neurogenetics, Kennedy Krieger Institute, Baltimore, Maryland; Departments of Neurology and Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York. Electronic address: augustinee@kennedykrieger.org. FAU - Adams, Heather R AU - Adams HR AD - Departments of Neurology and Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York. FAU - de Los Reyes, Emily AU - de Los Reyes E AD - Department of Pediatrics and Neurology, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio. FAU - Drago, Kristen AU - Drago K AD - Hospice Consultant, Lake Zurich, Illinois. FAU - Frazier, Margie AU - Frazier M AD - Rare Disease Advocate and Consultant, Columbus, Ohio. FAU - Guelbert, Norberto AU - Guelbert N AD - Metabolic Diseases Section, Children's Hospital of Cordoba, Cordoba, Argentina. FAU - Laine, Minna AU - Laine M AD - Department of Pediatric Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. FAU - Levin, Tanya AU - Levin T AD - Medical Writing Consultant, Atlanta, Georgia. FAU - Mink, Jonathan W AU - Mink JW AD - Departments of Neurology, Neuroscience, and Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York. FAU - Nickel, Miriam AU - Nickel M AD - Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Peifer, Danielle AU - Peifer D AD - Nationwide Children's Hospital, Columbus, Ohio. FAU - Schulz, Angela AU - Schulz A AD - Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Simonati, Alessandro AU - Simonati A AD - Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona School of Medicine, Verona, Italy. FAU - Topcu, Meral AU - Topcu M AD - Professor Emeritus, Department of Pediatric Neurology, Hacettepe University, Ankara, Turkey. FAU - Turunen, Joni A AU - Turunen JA AD - Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. FAU - Williams, Ruth AU - Williams R AD - Children's Neurosciences Centre, Evelina London Children's Hospital, London, United Kingdom. FAU - Wirrell, Elaine C AU - Wirrell EC AD - Divisions of Epilepsy and Child and Adolescent Neurology, Department of Neurology, Mayo Clinic, Rochester, Minnesota. FAU - King, Sharon AU - King S AD - Taylor's Tale, Charlotte, North Carolina. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210409 PL - United States TA - Pediatr Neurol JT - Pediatric neurology JID - 8508183 RN - 0 (Membrane Proteins) RN - EC 3.1.2.- (Thiolester Hydrolases) RN - EC 3.1.2.22 (PPT1 protein, human) RN - Ceroid lipofuscinosis, neuronal 1, infantile SB - IM MH - Adolescent MH - Caregivers MH - Child MH - Child, Preschool MH - *Consensus MH - Disease Progression MH - Humans MH - Infant MH - Membrane Proteins MH - Neuronal Ceroid-Lipofuscinoses/*complications/*diagnosis/*therapy MH - Palliative Care MH - Phenotype MH - Practice Guidelines as Topic/*standards MH - Rare Diseases MH - Stakeholder Participation MH - Thiolester Hydrolases OTO - NOTNLM OT - Clinical care OT - Drug-resistant epilepsy OT - Infantile neuronal ceroid lipofuscinosis OT - Lysosomal storage disease OT - PPT1 OT - Palliative care OT - Palmitoyl-protein thioesterase 1 OT - Rare disease EDAT- 2021/05/18 06:00 MHDA- 2022/02/03 06:00 CRDT- 2021/05/17 20:20 PHST- 2020/09/04 00:00 [received] PHST- 2021/04/01 00:00 [revised] PHST- 2021/04/04 00:00 [accepted] PHST- 2021/05/18 06:00 [pubmed] PHST- 2022/02/03 06:00 [medline] PHST- 2021/05/17 20:20 [entrez] AID - S0887-8994(21)00069-2 [pii] AID - 10.1016/j.pediatrneurol.2021.04.002 [doi] PST - ppublish SO - Pediatr Neurol. 2021 Jul;120:38-51. doi: 10.1016/j.pediatrneurol.2021.04.002. Epub 2021 Apr 9.