The LINCE Project: A Pathway for Diagnosing NCL2 Disease

• DOI: 10.3389/fped.2022.876688
• Publication Date: 2022-03-30T04:52:48Z
• Authors: Daniel Rodrigues; Maria José de Castro; Pablo Crujeiras; Anna Duat-Rodriguez; Ana Victoria Marco; Mireia del Toro; María L. Couce; Cristóbal Colón
• Keywords: :diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::cribado neonatal [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]; screening tripeptidyl peptidase 1; :Nervous System Diseases::Neurodegenerative Diseases::Heredodegenerative Disorders, Nervous System::Neuronal Ceroid-Lipofuscinoses [DISEASES]; Medicina; enzymatic activity; :Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Neonatal Screening [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]; :Otros calificadores::/diagnóstico [Otros calificadores]; dried blood spot; Pediatrics; Sistema nerviós - Degeneració; RJ1-570; 3. Good health; 03 medical and health sciences; :diagnóstico::diagnóstico precoz [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]; 0302 clinical medicine; :enfermedades del sistema nervioso::enfermedades neurodegenerativas::trastornos heredodegenerativos del sistema nervioso::lipofuscinosis ceroide neuronal [ENFERMEDADES]; Cribatge (Medicina); :Other subheadings::/diagnosis [Other subheadings]; Malalties congènites - Diagnòstic; Infants; NCL2 disease; :Diagnosis::Early Diagnosis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]; early diagnosis

IntroductionNeuronal 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.MethodsIn 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).ResultsOver 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.ConclusionsLINCE 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.