The LINCE Project: A Pathway for Diagnosing NCL2 Disease.

Fecha de publicación: 29/03/2022 Fecha Ahead of Print: 29/03/2022

Autores de IIS La Fe

Ana Victoria Marco Hernández

Autor

Participantes ajenos a IIS La Fe

Rodrigues, Daniel
de Castro, Maria Jose
Crujeiras, Pablo
Duat-Rodriguez, Anna
del Toro, Mireia
Couce, Maria L.
Colon, Cristobal

Grupos

Investigación Traslacional en Genética

Leader

Francisco Martínez Castellano

Abstract

INTRODUCTION: Neuronal Ceroid Lipofuscinosis (NCL) comprises a clinically and genetically heterogeneous group of 13 neurodegenerative lysosomal storage disorders. Neuronal Ceroid lipofuscinosis type 2 disease (NCL2), caused by the deficient lysosomal enzyme tripeptidyl peptidase 1 (TPP1), is the only one with an approved enzyme replacement treatment (ERT). Early initiation of ERT appears to modify significantly the natural history of the disease. We aimed to shorten the time to diagnosis of NCL2. METHODS: In March 2017, we started per first time in Spain a selective screening program, the LINCE project, in pediatric patients with clinical symptoms compatible with NCL2 disease. The program covered the whole country. We distributed kits to pediatricians with the necessary material to assess patients. All samples in this study were received within one week of collection. Enzymatic activity determined on dried blood spots was the main method used to screen for TPP1 and palmitoyl protein thioesterase 1 (PPT1) for the differential diagnosis with neuronal ceroid lipofuscinosis type 1 (NCL1). RESULTS: Over a period of three years, we received 71 samples. The analysis was minimally invasive, relatively cheap and fast-executing. Three cases identified as a direct result of the selective screening strategy were confirmed by genetic study of NCL2 disease with a median age of 4.5 years. Our screening method has a specificity of 100%, and, with the absence to date of false negatives. We did not detect any NCL1-positive cases. CONCLUSIONS: LINCE proved to be a simple, useful, and reliable tool for the diagnosis of NCL2, enabling clinicians to diagnose NCL2 faster. The presence of NCL2-positive cases in our population and availability of treatment may facilitate the inclusion of NCL2 in neonatal screening programs for early diagnosis.

Datos de la publicación

ISSN/ISSNe:: 2296-2360, 2296-2360
Tipo:: Article
Páginas:: 876688-876688
DOI:: 10.3389/fped.2022.876688
PubMed:: 35425725
Factor de Impacto:: 0,850 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Rodrigues, Daniel:: Congenital Metabolic Diseases Unit, Department of Neonatology, University Clinical Hospital of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago (IDIS), European Reference Network for Hereditary Metabolic Disorders (MetabERN), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), Santiago de Compostela, Spain

Department of Pediatrics, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain
de Castro, Maria Jose:: Congenital Metabolic Diseases Unit, Department of Neonatology, University Clinical Hospital of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago (IDIS), European Reference Network for Hereditary Metabolic Disorders (MetabERN), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), Santiago de Compostela, Spain
Crujeiras, Pablo:: Congenital Metabolic Diseases Unit, Department of Neonatology, University Clinical Hospital of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago (IDIS), European Reference Network for Hereditary Metabolic Disorders (MetabERN), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), Santiago de Compostela, Spain

Department of Pediatrics, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain
Duat-Rodriguez, Anna:: Department of Neuropediatrics, Niño Jesús Children's Hospital, Madrid, Spain
Marco, Ana Victoria:: Genomics Unit, La Fe University and Polytechnic Hospital, Valencia, Spain
del Toro, Mireia:: Pediatric Neurology Unit, Vall D'Hebron University Hospital, Barcelona, Spain
Couce, Maria L.:: Congenital Metabolic Diseases Unit, Department of Neonatology, University Clinical Hospital of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago (IDIS), European Reference Network for Hereditary Metabolic Disorders (MetabERN), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), Santiago de Compostela, Spain

Department of Pediatrics, Faculty of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain
Colon, Cristobal:: Congenital Metabolic Diseases Unit, Department of Neonatology, University Clinical Hospital of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago (IDIS), European Reference Network for Hereditary Metabolic Disorders (MetabERN), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), Santiago de Compostela, Spain

Keywords

NCL2 disease; dried blood spot; early diagnosis; enzymatic activity; screening tripeptidyl peptidase 1

Proyectos y Estudios Clínicos