Natural History of Neuronal Ceroid Lipofuscinosis Type 6, Late Infantile Disease.

Autor: O'Neal M; Department of Pediatric Neurology, Nationwide Children's Hospital, Columbus, Ohio., Noher de Halac I; Consultant Professor, National University of Cordoba, Córdoba, Argentina., Aylward SC; Department of Pediatric Neurology, Nationwide Children's Hospital, Columbus, Ohio; The Ohio State University College of Medicine, Columbus, Ohio., Yildiz V; Biostatistics Resource at Nationwide Children's Hospital (BRANCH), Nationwide Children's Hospital, Columbus, Ohio; Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio., Zapanta B; Division of Molecular and Human Genetics, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio., Abreu N; Department of Neurology, NYU Grossman School of Medicine, New York, New York., de Los Reyes E; Department of Pediatric Neurology, Nationwide Children's Hospital, Columbus, Ohio; The Ohio State University College of Medicine, Columbus, Ohio. Electronic address: Emily.delosReyes@nationwidechildrens.org.
Jazyk: angličtina
Zdroj: Pediatric neurology [Pediatr Neurol] 2024 May; Vol. 154, pp. 51-57. Date of Electronic Publication: 2024 Mar 01.
DOI: 10.1016/j.pediatrneurol.2024.02.010
Abstrakt: Background: Mutations in the CLN6 gene cause late infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disease of childhood onset. Clinically, individuals present with progressive motor and cognitive regression, ataxia, and early death. The aim of this study is to establish natural history data of individuals with classic, late-infantile-onset (age less than five years) CLN6 disease.
Methods: We analyzed the natural history of 25 patients with late-infantile-onset CLN6, utilizing the Hamburg motor-language scale to measure disease progression. The key outcomes were CLN6 disease progression, assessed by rate of decline in motor and language clinical domain summary scores (0 to 6 total points); onset and type of first symptom; onset of first seizure; and time from first symptom to complete loss of function.
Results: Median age of total motor and language onset of decline was 42 months (interquartile range 36 to 48). The estimated rate of decline in total score was at a slope of -1.20 (S.D. 0.30) per year, after the start of decline. Complete loss of both motor and language function was found to be, on average, 88.1 months (S.D. 13.5).
Conclusions: To our knowledge, this is the largest international study that monitors the longitudinal natural history and progression of CLN6 disease. These data may serve as a template for future interventional trials targeted to slow the progression of this devastating disease.
Competing Interests: Declaration of competing interest E.d.l.R. has grant/contract support with BioMarin and Amicus Therapeutics, royalties with Amicus Therapeutics, consulting fees with Amicus Therapeutics, and payments/honoraria for lectures, presentations, and educational events with Amicus Therapeutics and BioMarin. S.A. has grant/contract support with BioMarin, Amicus Therapeutics, Pfizer and NeuroNEXT/NINDS/The Ohio State University; consulting fees with National Vaccine Injury Compensation Program; and payments/honoraria as associate editor for Pediatric Neurology. I.N.d.H. has grant/contract support with Grant Proyecto de Investigacion y Desarrollo Clínico-PID-C from the Ministerio de Ciencia y Tecnología de la Nación, Argentina; Grant of the Batten Disease Support Research Association – BDSRA; Grants of the Consejo Nacinal de Investigaciones Cientificas y Técnicas de la Republica Argentina – CONICET; and Grants of the Secretaria de Ciencia y Tecnología – Universidad Nacional de Córdoba, Argentina – SECYT-UNC. N. Abreu has grant/contract support with BioMarin and Amicus Therapeutics.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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