Neuronal Ceroid-Lipofuscinoses, Neuronal Ceroid Lipofuscinosis CLN2, Spinocerebellar Ataxia, Autosomal Recessive 7
Conditions
Keywords
Neuronal Ceroid Lipofuscinosis, Atypical CLN2 Disease, Natural History
Brief summary
The purpose of this study is to gather information on the possible symptoms that patients with atypical neuronal ceroid lipofuscinosis type 2 (also known as aTPP1 or atypical tripeptidyl peptidase deficiency) have and how they change over time.
Detailed description
This study aims characterize the natural history of atypical TPP1 deficiency patients via longitudinal multidisciplinary assessments. Multifaceted clinical, laboratory, imaging, and diagnostic assessments will be performed at regular intervals upon enrolled aTPP1 deficiency patients, collated, and analyzed over a three-year longitudinal period.
Interventions
None listed
Sponsors
Children's Hospital of Orange County
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Any patient with documented TPP1 enzymatic deficiency or TPP1 sequence variants * Onset of first symptom after 4 years of age * Parental provision of informed consent; child provision of assent (if necessary)
Exclusion criteria
* Any patient with "Classical" TPP1 deficiency (onset of first symptom prior to 4 years of age) * Investigator assessment that patient is not suitable candidate to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CLN2 Disease Severity Scoring | At baseline and every 3 months afterwards, up to 3 years | Modified Hamburg Rating Scale. The rating scale consists of two domains (motor function, language). Within each domain, a score from 0 to 3 is assigned and overall scores are calculated by summing the domain scores for final rating of 0 (severely impaired) to 6 (normal). |
| Electroretinogram (ERG) | At baseline and every 6 months afterwards, up to 3 years | Standard ERG will be performed to measure function of cones and rods of the inner and outer photoreceptor layers which amplitudes are typically decreased in classical TPP1 deficiency. |
| Optical Coherence Tomography (OCT) | At baseline and every 6 months afterwards, up to 3 years | OCT is non-invasive, quantitative measurement of inner and outer photoreceptor layer thicknesses. |
| Gait Assessment | At baseline and every 6 months afterwards, up to 3 years | Gait assessment is acquired utilizing infrared sensors applied to participant's clothing and will include collection of walking speed, cadence, swing phase, stride length and time, walking base width, stance phase, and double limb support phase. |
| Brain Magnetic Resonance Imaging (MRI) | At baseline and every 12 months afterwards, up to 3 years | Pre/post-contrast images will be acquired to perform volumetric studies and white matter assessment. |
| Electroencephalography (EEG) | At baseline and every 12 months afterwards, up to 3 years | EEG will be obtained and analyzed for changes that may be distinctive for TPP1 deficiency. Evaluation of background activity, mild/moderate/severe slowing for age. |
| Cognitive Assessment, Wechsler Intelligence Scale for Children version 4 (WISC-IV) | At baseline and every 12 months afterwards, up to 3 years | WISC-IV will generate a full scale of intelligence quotient and five primary index scores: Verbal Comprehension, Visual Spatial, Fluid Reasoning, Working Memory, and Processing Speed. The WAIS-IV is scored by summing the raw scores for each subtest; each raw subtest score is then converted to a scaled scored. They are then combined to create a Full Scale IQ Index score. Test takers will also be given a score on the General Ability Index (GAI). |
| CSF Testing | At baseline and every 3 months afterwards, up to 3 years | Standard laboratory testing and biobanking / storage of remaining CSF (via Ommaya if on enzyme replacement; via lumbar puncture if not on enzyme replacement) |
Countries
United States
Outcome results
None listed