Longitudinal Assessment of Atypical Tripeptidyl Peptidase 1 Enzyme Deficiency Patients

Study Overview
=================
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.

Official Title
-----------------
Longitudinal Assessment of Atypical Tripeptidyl Peptidase 1 Enzyme Deficiency (Neuronal Ceroid Lipofuscinosis Type 2) Patients

Conditions
-----------------
Neuronal Ceroid-Lipofuscinoses, Neuronal Ceroid Lipofuscinosis CLN2, Spinocerebellar Ataxia, Autosomal Recessive 7

Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 4 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CLN2 Disease Severity Scoring | 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). | At baseline and every 3 months afterwards, up to 3 years | 
| Electroretinogram (ERG) | 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. | At baseline and every 6 months afterwards, up to 3 years | 
| Optical Coherence Tomography (OCT) | OCT is non-invasive, quantitative measurement of inner and outer photoreceptor layer thicknesses. | At baseline and every 6 months afterwards, up to 3 years | 
| Gait Assessment | 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. | At baseline and every 6 months afterwards, up to 3 years | 
| Brain Magnetic Resonance Imaging (MRI) | Pre/post-contrast images will be acquired to perform volumetric studies and white matter assessment. | At baseline and every 12 months afterwards, up to 3 years | 
| Electroencephalography (EEG) | 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. | At baseline and every 12 months afterwards, up to 3 years | 
| Electroencephalography (EEG) | EEG will be obtained and analyzed for changes that may be distinctive for TPP1 deficiency. Interictal discharges: location, focal/generalized, discharge burden. | At baseline and every 12 months afterwards, up to 3 years | 
| Electroencephalography (EEG) | Seizures. | At baseline and every 12 months afterwards, up to 3 years | 
| Electroencephalography (EEG) | Photoparoxysmal response: present/absent | At baseline and every 12 months afterwards, up to 3 years | 
| Cognitive Assessment, Wechsler Intelligence Scale for Children version 4 (WISC-IV) | 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). | At baseline and every 12 months afterwards, up to 3 years | 
| CSF Testing | Standard laboratory testing and biobanking / storage of remaining CSF (via Ommaya if on enzyme replacement; via lumbar puncture if not on enzyme replacement) | At baseline and every 3 months afterwards, up to 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neuronal Ceroid Lipofuscinosis, Atypical CLN2 Disease, Natural History