Observational studyThe Lancet. Child & adolescent health2018
Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study.
Observational study in The Lancet. Child & adolescent health, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04613089 (Natural History and Long Term Clinical Assessments of All Forms of Neuronal Ceroid Lipofuscinoses - Capturing Key Symptoms and Disease Progression as Part of the Independent, International NCL DEM-CHILD Patient Database), which is not on this map. Cited by 79 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Natural History and Long Term Clinical Assessments of All Forms of Neuronal Ceroid Lipofuscinoses - Capturing Key Symptoms and Disease Progression as Part of the Independent, International NCL DEM-CHILD Patient Database
Who cites it
79 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Psychiatric manifestations in Neuronal ceroid lipofuscinoses.Orphanet journal of rare diseases · 2026Pooled it
- Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients.Orphanet journal of rare diseases · 2021Pooled it
- Exploring concurrent validity of the CLN2 Clinical Rating Scale: Comparison to PedsQL using cerliponase alfa clinical trial data.PloS one · 2024Trial
- Slowing late infantile Batten disease by direct brain parenchymal administration of a rh.10 adeno-associated virus expressingScience translational medicine · 2020Trial
- Epilepsy Is Part of the CNS Phenotype in Classic Infantile Pompe Disease.Neurology. Genetics · 2026Article
- Conversion of a ventricular rickham reservoir to a subcutaneous chest port for repeated intraventricular enzyme replacement therapy: technical note and surgical considerations.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Article
- Review
- Patient and Family Perspective on Transition from Ventricular Access Device to Chest-Sited Port for Intracerebroventricular Infusion in CLN2 Disease.Children (Basel, Switzerland) · 2026Article
- Age at onset and gene variants predict lifespan and disease duration in childhood neuronal ceroid lipofuscinoses.Developmental medicine and child neurology · 2026Article
- Bioenergetic Profiling Applied to a Zebrafish Model of Neuronal Ceroid Lipofuscinosis, a Lysosomal Storage Disorder.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Chronic oral cannabidiol delays seizure onset and reduces seizure burden in a mouse model of CLN2 disease.PloS one · 2026Article
- Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.Nature reviews. Neurology · 2025Review
- Assessment of motor deterioration in a cynomolgus macaque with neuronal ceroid lipofuscinosis type 2 disease using two behavioral analyses.The Journal of veterinary medical science · 2025Article
- Trial Readiness: Understanding the Natural History of Rare Diseases.Journal of inherited metabolic disease · 2025Review
- Seizures and electroencephalographic findings in inborn errors of metabolism: Clues to differential diagnosis in the neonatal period, infancy, childhood and adolescence, and review of the literature.Epileptic disorders : international epilepsy journal with videotape · 2025Review
- The Wechsler intelligence scale for children, fourth and fifth editions perform comparably in children with Batten disease.Orphanet journal of rare diseases · 2025Article
- Benchmarking Nanopore Sequencing for CLN2 (TPP1) Mutation Detection: Integrating Rapid Genomics and Orthogonal Validation for Precision Diagnostics.International journal of molecular sciences · 2025Article
- Evidence of the impact of CLN2 and CLN3 Batten disease on families in the United Kingdom.Orphanet journal of rare diseases · 2025Article
- Intravitreal Enzyme Replacement Therapy Slows Retinopathy in Late Infantile Ceroid Lipofuscinosis Type 2.Neuropediatrics · 2025Article
- Neuronal Ceroid Lipofuscinosis-Concepts, Classification, and Avenues for Therapy.CNS neuroscience & therapeutics · 2025Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
16 authors.
Funding
Abstract
backgroundLate-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease, characterised by rapid psychomotor decline and epilepsy, is caused by deficiency of the lysosomal enzyme tripeptidyl peptidase 1. We aimed to analyse the characteristics and rate of progression of CLN2 disease in an international cohort of patients.
methodsWe did an observational cohort study using data from two independent, international datasets of patients with untreated genotypically confirmed CLN2 disease: the DEM-CHILD dataset (n=74) and the Weill Cornell Medical College (WCMC) dataset (n=66). Both datasets included quantitative rating assessments with disease-specific clinical domain scores, and disease course was measured longitudinally in 67 patients in the DEM-CHILD cohort. We analysed these data to determine age of disease onset and diagnosis, as well as disease progression-measured by the rate of decline in motor and language summary scores (on a scale of 0-6 points)-and time from first symptom to death.
findingsIn the combined DEM-CHILD and WCMC dataset, median age was 35·0 months (IQR 24·0-38·5) at first clinical symptom, 37·0 months (IQR 35·0 -42·0) at first seizure, and 54·0 months (IQR 47·5-60·0) at diagnosis. Of 74 patients in the DEM-CHILD dataset, the most common first symptoms of disease were seizures (52 [70%]), language difficulty (42 [57%]), motor difficulty (30 [41%]), behavioural abnormality (12 [16%]), and dementia (seven [9%]). Among the 41 patients in the DEM-CHILD dataset for whom longitudinal assessments spanning the entire disease course were available, a rapid annual decline of 1·81 score units (95% CI 1·50-2·12) was seen in motor-language summary scores from normal (score of 6) to no function (score of 0), which occurred over approximately 30 months. Among 53 patients in the DEM-CHILD cohort with available data, the median time between onset of first disease symptom and death was 7·8 years (SE 0·9) years.
interpretationIn view of its natural history, late-infantile CLN2 disease should be considered in young children with delayed language acquisition and new onset of seizures. CLN2 disease has a largely predictable time course with regard to the loss of language and motor function, and these data might serve as historical controls for the assessment of current and future therapies.
fundingEU Seventh Framework Program, German Ministry of Education and Research, EU Horizon2020 Program, National Institutes of Health, Nathan's Battle Foundation, Cures Within Reach Foundation, Noah's Hope Foundation, Hope4Bridget Foundation.
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