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The LINCE Project: A Pathway for Diagnosing NCL2 Disease

Authors :: Rodrigues, Daniel
de Castro, María José
Crujeiras, Pablo
Duat Rodriguez, Anna
Marco Hernández, Ana Victoria
del Toro Riera, Mireia
Couce, Maria Luz
Colón, Cristóbal
Institut Català de la Salut
[Rodrigues D, Crujeiras P, Couce ML] 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 MJ, Colón C] 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. [Duat-Rodriguez A] Department of Neuropediatrics, Niño Jesús Children’s Hospital, Madrid, Spain. [Marco AV] Genomics Unit, La Fe University and Polytechnic Hospital, Valencia, Spain. [Del Toro M] Servei de Neurologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
Source :: Scientia
Publication Year :: 2022
Abstract: NCL2 disease; Dried blood spot; Enzymatic activity Enfermedad de NCL2; Mancha de sangre seca; Actividad enzimática Malaltia de NCL2; Taca de sang seca; Activitat enzimàtica 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. This study received funding from Grant Biomarin Inc. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.