Gs-UNIT ACTIVITY IN PSEUDOHYPOPARATHYROIDISM SYNDROME: RESULTS OF A PEDIATRIC MULTICENTER STUDY

Pseudohypoparathyroidism (PsHP) is a rare disorder that might be caused by a defect in the stimulatory G-proteine (Gs), which transduce the PTH receptor signal to adenylate cyclase. We investigate 35 patients (29 children and 6 adults) with PsHP syndrome. Clinical features, Ellsworth-Howard test, serum level of intact PTH (PTHi) and Gs biological activity are studied. Gs activity is measured with a technic adapted from that of LEVINE we optimized to applicate in children (Assay variation : 10 %). 24 patients (68 %) have a PsHP type Ia with a decrease of Gs-unit activity, but we don't find any relation between Albright's osteodystrophy (AHO) and Gs-unit defect : 4 children are AHO - and 20 are AHO +, and 10 of them presented an associate hypothyroidism. 2 patients (6 %) have no response to infusion of exogenous PTH with an increased of Gs-unit activity and could be PsHP type Ib. Only one patient is PsHP type II with normal Gs-unit, serum PTHi level are increased in all patients (mean = 218 pg/ml, range 65 - 571) without difference between PsHP groups, or relation with Gs-unit activity. Other patients would be classified in pseudo-PsHP with decrease Gs - biological activity. In other hand, we studied 10 families, in 9 Gs-unit activity defect is found at least in 1 member (7 times mother, 1 both mother and father, 1 father). In conclusion, Gs-unit activity appears to be of interest in the investigation of PsHP syndrome.