PREPL in Health and Disease (PHD)

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.

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

Patients with symptoms overlapping with primary PREPL deficiency (like hypotonia, growth hormone deficiency, obesity), blood draw

Patients without hypotonia, growth hormone deficiency, obesity, undergoing elective surgery, muscle biopsy from the surgical site and blood draw

Patients with Prader-Willi syndrome undergoing elective anesthesia or surgery, muscle biopsy (from surgical site if applicable) and blood draw

PREPL activity in patients with muscle weakness/obesity/growth hormone deficiency compared to activity in normal controls

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

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.

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.