investigations of juvenile neuronal ceroid lipofuscinosis

Conditions: Juvenile Neuronal Ceroid Lipofuscinosis (CLN3); Batten Disease

Summary: background: cln3, or batten disease, is a genetic disorder. this deadly disease leads to decline of brain and nervous system functions. symptoms of cln3 typically occur between 4 and 7 years of age. they include changes in how a person sees, thinks, and moves. cln3 can also cause seizures. no effective treatments for the disease are yet known. there is limited testing of potential therapies. researchers want to study cln3 more so they can improve future therapies. objective: to identify clinical or biochemical markers that can be used as therapeutic outcome measures for cln3. eligibility: people with cln3. it must be based on two cln3 mutations or one cln3 mutation and findings seen with a powerful microscope family members of a person with cln3. design: participants will have already been referred to nih for cln3 evaluation. if participants agree to do the study, they will: 1. give spinal fluid, blood, urine, and skin samples. they may provide other samples if they were already collected. these may include cells, surgical specimens, and dna. 2. will be seen by multiple healthcare specialists. participants may provide medical records or photos. participants will sign a release of medical records form.p researchers may send samples or clinical data to other investigators. for research testing, the samples will not include the participant s name. for a test in a clinical lab, researchers will include the participant s name. these results will become part of the clinical record at nih.

study description: the purpose of this protocol is to obtain both baseline and rate of progression data on clinical and biochemical markers that may later be used as an outcome measure in a clinical trial, and to establish a biorepository of samples from cln3 participants. for comparisons, focused clinical data and relevant evaluations and biospecimens will also be collected from individuals with neuronal ceroids lipofuscinosis (ncl) of other types and from family members of all affected individuals. objectives: primary objective: 1. identify clinical or biochemical markers that can be used as therapeutic outcome measures for cln3. 2. evaluate clinical aspects of cln3 to provide tools for future therapeutic trials. secondary objectives: establish a biorepository of samples from well-characterized individuals with cln3, and family members of cln3 individuals, for future research related to cln3. endpoints: primary endpoint: 1. blood, urine, or csf biomarkers. 2. proportion of participants who achieve a clinically valid and interpretable score on administered measures. 3. scores obtained for each administered measure. secondary endpoints: tolerability and feasibility of each measure of the clinical battery of assessments based on clinician observation.

Eligibility criteria:
* inclusion criteria: for the main and sub-studies, participants \> 1 week of age, of all genders, demographics, geographic locations, and disease severity will be recruited in order to obtain cross-sectional representation of cln3 (main and sub-studies) or all ncls (sub-study b). participants in the main study will be followed at approximately yearly intervals to obtain longitudinal data. participants in sub-study a may elect to send in medical records and samples only, or to come to the nih for evaluations as outlined in section 4. we anticipate that participants in sub-study b will be seen mostly at ncl/cln3-related family conferences. main study: individuals \> 1 week of age with a diagnosis of cln3. diagnosis of cln3 determined by one of the following: 1. two cln3 mutations 2. one cln3 mutation and i) clinical presentation suggestive of cln3, or ii) characteristic electron microscopy (em) findings (such as curvilinear body, fingerprint profile, granular osmiophilic deposits). sub-study a: individuals \> 1 week of age with a diagnosis of cln3. diagnosis of cln3 determined by one of the following: 1. two cln3 mutations 2. one cln3 mutation and i) clinical presentation suggestive of cln3, or ii) characteristic electron microscopy (em) findings (such as curvilinear body, fingerprint profile, granular osmiophilic deposits). or individuals \> 1 month of age who have family member(s) diagnosed with cln3 sub-study b: individuals \> 1 week of age with a clinical diagnosis of cln3 or ncl. or individuals \> 1 month of age who have family member(s) diagnosed with cln3 or ncl. exclusion criteria: main study: 1. individuals who cannot travel to the nih because of their medical condition. 2. individuals who, in the opinion of the investigator, are unable to comply with the protocol or have medical conditions that would potentially increase the risk of participation. 3. females who are pregnant. sub-studies a and b: 1. unaffected individuals \> 18 years of age who have cognitive impairments. 2. individuals who, in the opinion of the investigator, are unable to comply with the protocol or have medical conditions that would potentially increase the risk of participation.

Keywords: batten disease neurodegenerative lysosomal storage biomarkers longitudinal study natural history