학술논문
Newborn screening for primary carnitine deficiency: who will benefit? - a retrospective cohort study.
Document Type
Academic Journal
Author
Crefcoeur L; Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands l.l.crefcoeur@umcutrecht.nl.; Department of Pediatrics, Division of Metabolic Disorders, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.; Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam UMC Locatie Meibergdreef, Amsterdam, The Netherlands.; Ferdinandusse S; Department of Pediatrics, Division of Metabolic Disorders, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.; Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam UMC Locatie Meibergdreef, Amsterdam, The Netherlands.; van der Crabben SN; Human Genetics, Amsterdam UMC Locatie Meibergdreef, Amsterdam, The Netherlands.; United for Metabolic Diseases, Amsterdam, The Netherlands.; Dekkers E; Centre for Population Screening, RIVM, Bilthoven, The Netherlands.; Fuchs SA; Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands.; Huidekoper H; Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus Medical Center, Rotterdam, The Netherlands.; Janssen M; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.; Langendonk J; Department of Internal Medicine, Center for Lysosomal and Metabolic Diseases, Erasmus Medical Center, Rotterdam, The Netherlands.; Maase R; Department of Biologicals, Screening and Innovation, RIVM, Bilthoven, The Netherlands.; de Sain M; Section Metabolic Diagnostics, Department of Genetics, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands.; Rubio E; Department of Pediatrics/Laboratory of Clinical Genetics, Maastricht UMC+, Maastricht, The Netherlands.; van Spronsen FJ; Section of Metabolic Diseases, University Medical Centre Groningen, Beatrix Children's Hospital, Groningen, The Netherlands.; Vaz FM; Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Departments of Clinical Chemistry and Pediatrics, Core Facility Metabolomics, Emma Children's Hospital, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Locatie Meibergdreef, Amsterdam, The Netherlands.; Verschoof R; Department for Vaccine Supply and Prevention Programs, RIVM, Bilthoven, The Netherlands.; de Vries M; Department of Pediatrics, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.; Wijburg F; Department of Pediatrics, Division of Metabolic Disorders, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.; Visser G; Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands.; Department of Pediatrics, Division of Metabolic Disorders, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.; Langeveld M; Department of Endocrinology and Metabolism, Amsterdam UMC Locatie Meibergdreef, Amsterdam, The Netherlands.
Source
Publisher: British Medical Association Country of Publication: England NLM ID: 2985087R Publication Model: Electronic Cited Medium: Internet ISSN: 1468-6244 (Electronic) Linking ISSN: 00222593 NLM ISO Abbreviation: J Med Genet Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Newborn screening (NBS) programmes identify a wide range of disease phenotypes, which raises the question whether early identification and treatment is beneficial for all. This study aims to answer this question for primary carnitine deficiency (PCD) taking into account that NBS for PCD identifies newborns with PCD and also until then undiagnosed mothers.
Methods: We investigated clinical, genetic (variants in SLC22A5 gene) and functional (carnitine transport activity in fibroblasts) characteristics of all referred individuals through NBS (newborns and mothers) and clinically diagnosed patients with PCD (not through NBS). Disease phenotype in newborns was predicted using data from PCD mothers and cases published in literature with identical SLC22A5 variants.
Results: PCD was confirmed in 19/131 referred newborns, 37/82 referred mothers and 5 clinically diagnosed patients. Severe symptoms were observed in all clinically diagnosed patients, 1 newborn and none of the mothers identified by NBS. PCD was classified as severe in all 5 clinically diagnosed patients, 3/19 newborns and 1/37 mothers; as benign in 8/19 newborns and 36/37 mothers and as unknown in 8/19 newborns. Carnitine transport activity completely separated severe phenotype from benign phenotype (median (range): 4.0% (3.5-5.0)] vs 26% (9.5-42.5), respectively).
Conclusion: The majority of mothers and a significant proportion of newborns with PCD identified through NBS are likely to remain asymptomatic without early treatment. Conversely, a small proportion of newborns with predicted severe PCD could greatly benefit from early treatment. Genetic variants and carnitine transport activity can be used to distinguish between these groups.
Competing Interests: Competing interests: ML is involved in premarketing studies with Sanofi-Genzyme, Protalix BioTherapeutics and Idorsia, all in the field of Fabry disease. Financial arrangements are made through AMC Research BV. No fees, travel support or grants were obtained from pharmaceutical industry. FW is involved in premarketing studies with Lysogene and IntraBio. JL is involved in Phase III and IV trials initiated by Clinuvel, Ultragenyx and Alnylam, companies producing pharmaceutical drugs for other inherited metabolic diseases. FMV is a consultant for Scenic Biotech. All other authors declare that they have no potential conflicts of interest.
(© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)
Methods: We investigated clinical, genetic (variants in SLC22A5 gene) and functional (carnitine transport activity in fibroblasts) characteristics of all referred individuals through NBS (newborns and mothers) and clinically diagnosed patients with PCD (not through NBS). Disease phenotype in newborns was predicted using data from PCD mothers and cases published in literature with identical SLC22A5 variants.
Results: PCD was confirmed in 19/131 referred newborns, 37/82 referred mothers and 5 clinically diagnosed patients. Severe symptoms were observed in all clinically diagnosed patients, 1 newborn and none of the mothers identified by NBS. PCD was classified as severe in all 5 clinically diagnosed patients, 3/19 newborns and 1/37 mothers; as benign in 8/19 newborns and 36/37 mothers and as unknown in 8/19 newborns. Carnitine transport activity completely separated severe phenotype from benign phenotype (median (range): 4.0% (3.5-5.0)] vs 26% (9.5-42.5), respectively).
Conclusion: The majority of mothers and a significant proportion of newborns with PCD identified through NBS are likely to remain asymptomatic without early treatment. Conversely, a small proportion of newborns with predicted severe PCD could greatly benefit from early treatment. Genetic variants and carnitine transport activity can be used to distinguish between these groups.
Competing Interests: Competing interests: ML is involved in premarketing studies with Sanofi-Genzyme, Protalix BioTherapeutics and Idorsia, all in the field of Fabry disease. Financial arrangements are made through AMC Research BV. No fees, travel support or grants were obtained from pharmaceutical industry. FW is involved in premarketing studies with Lysogene and IntraBio. JL is involved in Phase III and IV trials initiated by Clinuvel, Ultragenyx and Alnylam, companies producing pharmaceutical drugs for other inherited metabolic diseases. FMV is a consultant for Scenic Biotech. All other authors declare that they have no potential conflicts of interest.
(© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)