Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database

Study Overview
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Brief Summary
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This is an observational study that aims at assessing the natural history of NCL diseases as part of the international DEM-CHILD Database. Patient data are collected from medical records, patient questionnaires and routine follow up clinical examinations with focus on assessing progression in key areas of disease such as motor, language, cognition, seizures, vision, and behavior. A local biorepository of samples from genetically defined NCL patients will be established as well as a virtual biorepository within the DEM-CHILD DB to be able to easily localize international availability of patient samples.

Detailed Description
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NCLs (Neuronal Ceroid Lipofuscinoses) are a group of rare, inherited, neurodegenerative disorders, also known as Batten disease. Until now, 13 different genes causing different subtypes of disease are known. The genetic mutations cause a symptom complex of progressive loss of acquired skills in the domains of motor function, cognition and visual function, leading to ataxia, movement disorder, dementia, blindness and seizures. In the area of genetic testing, variable clinical phenotypes become more and more prevalent. The disease-mechanisms as well as the exact clinical course of the diseases are currently still not fully understood and documented. Although descriptions of the clinical spectrums exist, the natural history needs to be defined as accurately as possible. These data are urgently needed as clinical control data helping to test the therapeutic efficacy of emerging experimental therapies. Since samples of genetically defined patients are rare and therefore limited for research, there is an urgent need for researchers to localize and access samples internationally. With the establishment of a local NCL-biorepository and virtual sample localization internationally, scientists worldwide may have a faster way to access needed samples for advancing research. Any NCL patient with a confirmed molecular diagnosis can join the retrospective and prospective natural history data collection. It is also possible for families with already deceased patients to participate in the retrospective analysis part of the data collection if the genetic mutation is known.

Official Title
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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

Conditions
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Neuronal Ceroid Lipofuscinosis, Batten Disease, CLN1 Disease, CLN2 Disease, CLN3 Disease, CLN4 Disease, CLN5 Disease, CLN6 Disease, CLN7 Disease, CLN8 Disease, CLN10 Disease, CLN11 Disease, CLN12 Disease, CLN13 Disease, CLN14 Disease

Intervention / Treatment
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* Other: Natural History


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patients with a confirmed molecular diagnosis of a form of NCL Disease Additional inclusion criteria for Group/Cohort: CLN2 Disease - ERT (Brineura) Treated: Documented diagnosis of TPP1 deficiency Previous or current treatment with intracerebroventricular ERT with cerliponase alpha Patients that are currently participating in post-marketing studies will be allowed to participate. Exclusion Criteria: - Patients with no confirmed molecular diagnosis of a form of NCL Disease
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CLN1 Disease, Haltia-Santavuori Disease<br>Patients with genetic mutations in the CLN1/PPT1 gene, causing a lysosomal enzyme deficiency of PPT1. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN2 Disease, Jansky-Bielschowsky Disease<br>Patients with genetic mutations in the CLN2/TPP1 gene, causing a lysosomal enzyme deficiency of TTP1. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN2 Disease - ERT (Brineura) treated<br>Patients with genetic mutations in the CLN2/TPP1 gene, causing a lysosomal enzyme deficiency of TTP1, previously and/or currently receiving enzyme-replacement therapy (ERT) with Cerliponase alpha (Brineura). | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN3 Disease, Spielmeyer-Vogt-Sjögren-Batten Disease<br>Patients with genetic mutations in the CLN3 gene. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN4 disease, Parry disease<br>Patients with genetic mutations in the CLN4/DNAJC5 gene. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN5 Disease<br>Patients with genetic mutations in the CLN5 gene. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN6 Disease, Kufs Disease Type A<br>Patients with genetic mutations in the CLN6 gene. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN7 Disease<br>Patients with genetic mutations in the CLN7/MFSD8 gene. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN8 Disease<br>Patients with genetic mutations in the CLN8 gene. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN10 Disease<br>Patients with genetic mutations in the CLN10/CTSD gene, causing a lysosomal enzyme deficiency of Cathepsin D. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN11 Disease<br>Patients with genetic mutations in the CLN11/GRN gene. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN12 Disease<br>Patients with genetic mutations in the CLN12/ATP13A2 gene. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN13 Disease, Kufs Disease Type B<br>Patients with genetic mutations in the CLN13/CTSF gene, causing a lysosomal enzyme deficiency of Cathepsin F. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|
| CLN14 Disease<br>Patients with genetic mutations in the CLN14/KCTD7 gene. | Other: Natural History<br>* Natural History and Clinical Follow Up.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of key symptoms of disease, natural history of disease progression and development of quantitative tools for rating disease progression that can be used as therapeutic outcome measures for emerging experimental therapies. | Evaluation of Medical history from patient interviews and medical chart review. Evaluating data from clinical routine follow up exams (e.g. brain imaging MRI, ophthalmologic assessments, OCT, EEG, cardiology assessments, cognitive assessments, developmental scales, clinical rating scales). | Up to 30 years | 
| Establish well characterized Natural History Cohorts from genetically defined NCL patients to provide these as Natural History Control Cohorts for new experimental therapy trials. | Analysis of retrospective and prospective data from patient interviews and medical chart review as well as clinical routine follow up exams (e.g. brain imaging MRI, ophthalmologic assessments, OCT, EEG, cardiology assessments, cognitive assessments, developmental scales, clinical rating scales). | Up to 30 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish a biorepository of samples from genetically defined NCL patients. | - Collection of biospecimens that have been collected within treatment as part of standard of care. | Up to 30 years | 
| Establish a virtual biorepository from genetically defined NCL patients within the DEM-CHILD Database. | Datacollection of available biospecimens from genetically defined NCL patients and the collecting center contacts within the DEM-CHILD DB. | Up to 30 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GRN, Neurodegenerative Diseases, Neurodegenerative Disorders, PME, EPMR, SCAR7, SGSH, PPT1, Haltia-Santavuori Disease, TPP1, Jansky-Bielschowsky Disease, Spielmeyer-Vogt-Sjögren-Batten Disease, DNAJC5, Parry Disease, Kufs Disease Type A, MFSD8, CTSD, ATP13A2, Kufor-Rakeb Syndrome, CTSF, Kufs Disease Type B, KCTD7, INCL, LINCL, VLINCL, JNCL, ANCL, NCL, CLN, Batten, Childhood Dementia, Lysosomal Storage Diseases, Metabolic Disorders