PREPL in Health and Disease

Study Overview
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Brief Summary
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Evaluation of PREPL activity in healthy controls and known or possible PREPL deficient patients

Detailed Description
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PREPL is defective in hypotonia cystinuria syndrome and in isolated PREPL deficiency. The investigators have constructed a blood test to evaluate PREPL activity in patients with possible PREPL deficiency. The study will determine normal values for age (0-18) for PREPL activity in blood. Also, patients with a clinical phenotype that overlaps with PREPL deficiency (including patients with known primary PREPL deficiency and Prader-Willi syndrome) will be evaluated for PREPL activity in blood. A last part of the study will involve muscle biopsies during elective anesthesia/surgery for other reasons. There will be 2 groups: patients without signs of PREPL deficiency undergoing surgery (controls) and patients with Prader-Willi syndrome undergoing anesthesia or surgery (patients). The control group will be age-matched to the hypotonia group. In the muscle biopsies, PREPL activity and expression will be evaluated.

Official Title
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PREPL in Health and Disease

Conditions
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Hypotonia-Cystinuria Syndrome, Muscle Hypotonia, Healthy Volunteers, Dwarfism, Growth Hormone Deficiency, Obesity, Prader-Willi Syndrome

Intervention / Treatment
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* Procedure: Blood draw
* Procedure: muscle biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: According to group Control group: children seen at a postinfectious consultation Exclusion Criteria: Control group: symptoms overlapping with PREPL deficiency, genetic or syndromic disease, atypically developing children other groups: contraindication for blood draw group with muscle biopsy: contra-indication for muscle biopsy

Ages Eligible for Study
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Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control Blood<br>Patients on routine postinfectious control, blood draw | Procedure: Blood draw<br>* Blood draw<br>|
| Experimental: Primary PREPL deficiency Blood<br>Patients with primary PREPL deficiency, blood draw | Procedure: Blood draw<br>* Blood draw<br>|
| Experimental: Prader Willi syndrome Blood<br>Patients with Prader-Willi syndrome, blood draw | Procedure: Blood draw<br>* Blood draw<br>|
| Experimental: Primary PREPL deficiency like Blood<br>Patients with symptoms overlapping with primary PREPL deficiency (like hypotonia, growth hormone deficiency, obesity), blood draw | Procedure: Blood draw<br>* Blood draw<br>|
| Experimental: Control muscle<br>Patients without hypotonia, growth hormone deficiency, obesity, undergoing elective surgery, muscle biopsy from the surgical site and blood draw | Procedure: Blood draw<br>* Blood draw<br>Procedure: muscle biopsy<br>* Muscle biopsy during planned anesthesia/surgery<br>|
| Experimental: Prader-Willli syndrome muscle<br>Patients with Prader-Willi syndrome undergoing elective anesthesia or surgery, muscle biopsy (from surgical site if applicable) and blood draw | Procedure: Blood draw<br>* Blood draw<br>Procedure: muscle biopsy<br>* Muscle biopsy during planned anesthesia/surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PREPL activity (ng active PREPL/g protein) normal values in blood | normal values for PREPL activity | 3 months | 
| PREPL activity in patients with Prader Willi syndrome compared to activity in normal controls | Comparison of PREPL activity in blood and muscle between above mentioned groups | 3 months | 
| PREPL activity in patients with primary PREPL deficiency compared to activity in normal controls | Comparison of PREPL activity in blood between above mentioned groups | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PREPL activity in patients with muscle weakness/obesity/growth hormone deficiency compared to activity in normal controls | exploratory evaluation | 3 months |