ObjectivePseudohypoparathyroidism type 1b (PHP1b) results from methylation defects in the maternal GNAS locus. It is implied that the observed hypocalcemia results from impairment of renal vitamin D 1α hydroxylase. This study was undertaken to clarify: (1) How serum concentrations of calcium, phosphate, PTH and 1,25 dihydroxy vitamin D (1,25OH2D) relate to each other in patients with PHP1b; (2) how a mathematical model of calcium metabolism could reproduce the observed findings. PatientsThe study included 139 untreated patients, retrieved from the literature, with simultaneous measurements of Ca, P and PTH of whom 25 had measurements of 1,25OH2D. ResultsMean values and standard errors of the mean (SEM) were: PTH=43pM (3.66); P=2.16mM (0.056); Ca=1.69mM (0.038); 1,25OH2D=84pM (10.9). Phosphate correlated negatively with calcium (R=−0.590; p<0.001) and with age (R=−0.623; p<0.001). No other correlations were observed. The mathematical model simulated closely the biochemical pattern of PHP1b when the clearance of phosphate was reduced to 20%, the clearance of calcium was doubled and the response of 1α hydroxylase was reduced to 30%. Conclusions(1) In PHP1b the concentrations of 1,25OH2D are mostly normal. Therefore, they cannot explain the observed hypocalcemia; (2) hypocalcemia can only be explained by increased fractional excretion of calcium resulting from GNAS haplo-insufficiency at the level of the distal tubule; (3) the use of mathematical models to simulate complex metabolic systems allows the extraction, from clinical data, of insights onto physiopathology that are not accessible to intuition alone.