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Published on: October 27, 2023
The LINCE Project: A Pathway for Diagnosing NCL2 Disease
Daniel Rodrigues1,2, Maria José de Castro1, Pablo Crujeiras1,2
1Congenital 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.
A new screening program, LINCE, successfully identified Neuronal Ceroid Lipofuscinosis type 2 (NCL2) in pediatric patients. This early diagnosis facilitates timely enzyme replacement treatment, improving patient outcomes for this rare neurodegenerative disorder.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Neurology
Background:
- Neuronal Ceroid Lipofuscinosis (NCL) is a group of 13 neurodegenerative lysosomal storage disorders.
- Neuronal Ceroid Lipofuscinosis type 2 (NCL2) is caused by deficient tripeptidyl peptidase 1 (TPP1) and is the only NCL with approved enzyme replacement treatment (ERT).
- Early ERT initiation significantly impacts NCL2 disease progression.
Purpose of the Study:
- To shorten the diagnostic timeline for NCL2.
- To implement and evaluate a nationwide selective screening program for NCL2 in Spain.
Main Methods:
- The LINCE project, a selective screening program, was initiated in Spain in March 2017 for pediatric patients with suspected NCL2.
- Dried blood spot analysis was used to measure TPP1 and PPT1 enzyme activity for NCL2 and NCL1 differential diagnosis.
- Kits were distributed to pediatricians nationwide for sample collection and assessment.
Main Results:
- Over three years, 71 samples were analyzed using a minimally invasive, cost-effective, and rapid method.
- Three NCL2 cases were confirmed via genetic testing, with a median diagnosis age of 4.5 years.
- The screening method demonstrated 100% specificity and no false negatives, with no NCL1 cases detected.
Conclusions:
- The LINCE project proved to be a simple, reliable tool for accelerating NCL2 diagnosis.
- Faster diagnosis enables earlier initiation of ERT, potentially altering the disease's natural history.
- Findings support the inclusion of NCL2 in neonatal screening programs due to identified cases and available treatment.
