Longitudinal Assessment of Atypical Tripeptidyl Peptidase 1 Enzyme Deficiency Patients

Primary outcomes

1. CLN2 Disease Severity Scoring

   Time frame: 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).

2. Electroretinogram (ERG)

   Time frame: 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.

3. Optical Coherence Tomography (OCT)

   Time frame: At baseline and every 6 months afterwards, up to 3 years

   OCT is non-invasive, quantitative measurement of inner and outer photoreceptor layer thicknesses.

4. Gait Assessment

   Time frame: 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.

5. Brain Magnetic Resonance Imaging (MRI)

   Time frame: 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.

6. Electroencephalography (EEG)

   Time frame: 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.

7. Electroencephalography (EEG)

   Time frame: 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. Interictal discharges: location, focal/generalized, discharge burden.

8. Electroencephalography (EEG)

   Time frame: At baseline and every 12 months afterwards, up to 3 years

   Seizures.

9. Electroencephalography (EEG)

   Time frame: At baseline and every 12 months afterwards, up to 3 years

   Photoparoxysmal response: present/absent

10. Cognitive Assessment, Wechsler Intelligence Scale for Children version 4 (WISC-IV)

    Time frame: 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).

11. CSF Testing

    Time frame: 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)