EVALUATION OF PLASMA SUBSTANCE P AND BETA-ENDORPHIN LEVELS IN CHILDREN WITH PRADER-WILLI SYNDROME.

Background: Prader-Willi syndrome (PWS) is a rare obesity-related genetic disorder often caused by a deletion of the chromosome 15q11-q13 region inherited from the father or by maternal disomy 15. Growth hormone deficiency with short stature, hypogonadism, cognitive and behavioral problems, analgesia, decreased gastric motility and decreased ability to vomit with hyperphagia are common in PWS leading to severe obesity in early childhood, if not controlled. Substance P (SP) and beta-endorphin (BE) are neuropeptides involved with centrally and peripherally mediated pain perception, emotional regulation, and gastric motility impacting nausea, emesis and feeding patterns.

Objective: The goal of this study was to investigate potential mechanisms for PWS symptom development for pain, emotion and gastric motility and plasma levels of substance P and beta-endorphin between PWS and unrelated unaffected children.

Methodology: Plasma samples were collected from 23 Caucasian children with PWS and 18 unrelated, unaffected siblings with an average age of 8.2 ±2.0 years and age range of 5 to 11 years following an overnight fast and neuropeptide substance p and beta-endorphin levels were assessed using Multiplex sandwich immunoassays using the Luminex magnetic-bead based platform. Linear regression analysis was carried out on log-transformed values adjusted for age, sex, and body mass index (BMI).

Results: The mean plasma SP (57 ± 23 pg/ml) and BE (592 ± 200 pg/ml) levels in PWS were significantly higher than SP (35 ± 20 pg/ml, F=10.5, P<0.01) and BE (402 ± 162 pg/ml, F=10.8, P<0.01) levels found in unrelated, unaffected siblings suggesting a previously uncharacterized neuroendocrine pathophysiology in PWS.

Conclusions: The increased BE and SP plasma levels relative to unrelated, unaffected siblings may contribute to hyperphagia, abnormal pain sensation and adrenal insufficiency seen in PWS. Increases in SP levels may be modulated by central and/or peripheral actions of BE on opioid, GABA or POMC precursors and may reflect loss of feedback inhibitory control. Further studies are needed to confirm and elucidate the biochemical basis for observed disturbances in neuropeptide levels seen in our study and may impact on the development and persistence of symptoms commonly seen in PWS.