Clinical trial NCT02263781: PREPL in Health and Disease
Official title: PREPL in Health and Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hypotonia-Cystinuria Syndrome
Muscle Hypotonia
Healthy Volunteers
Dwarfism, Growth Hormone Deficiency
Obesity
Prader-Willi Syndrome
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: KU Leuven
First posted: 2014-10-13
Enrollment: 125
Sex: ALL
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Evaluation of PREPL activity in healthy controls and known or possible PREPL deficient patients

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: PREPL activity (ng active PREPL/g protein) normal values in blood
timeFrame: 3 months
measure: PREPL activity in patients with Prader Willi syndrome compared to activity in normal controls
timeFrame: 3 months
measure: PREPL activity in patients with primary PREPL deficiency compared to activity in normal controls
timeFrame: 3 months
Secondary outcomes:
measure: PREPL activity in patients with muscle weakness/obesity/growth hormone deficiency compared to activity in normal controls
timeFrame: 3 months
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZLeuven
Study officials:
affiliation: KU Leuven
name: Luc Régal, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Regal L, Shen XM, Selcen D, Verhille C, Meulemans S, Creemers JW, Engel AG. PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome. Neurology. 2014 Apr 8;82(14):1254-60. doi: 10.1212/WNL.0000000000000295. Epub 2014 Mar 7.
citation: Jaeken J, Martens K, Francois I, Eyskens F, Lecointre C, Derua R, Meulemans S, Slootstra JW, Waelkens E, de Zegher F, Creemers JW, Matthijs G. Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome. Am J Hum Genet. 2006 Jan;78(1):38-51. doi: 10.1086/498852. Epub 2005 Nov 23.