The pathogenesis of
familial hypophosphatemic rickets (FHR) is incompletely understood. We therefore examined the effects of acute
dietary phosphorus deprivation to see whether renal
phosphate conservation and increased 1,25 dihydroxyvitamin D [1,25(
OH)2D] plasma levels, which normally follow restriction of
phosphorus intake, could be induced in patients with FHR. Six healthy male volunteers (age 26 +/- 3 yr) and seven male patients with FHR (age 24 +/- 3 yr) were placed on a low
phosphorus diet supplemented with
aluminum hydroxide and studied over a 4-d period. The patients with FHR excreted more than five times as much
phosphorus per day at the conclusion of the study than did the controls (176 +/- 61 mg/24 h vs. 33 +/- 11 mg/h). In the normal subjects, maximum tubular reabsorptive capacity for
phosphorus/glomerular filtration rate (
TmP/GFR) rose progressively during
phosphorus deprivation, and the rise from base line was more than two times greater than that seen in patients with FHR. Immunoreactive
parathyroid hormone levels and nephrogenous
cyclic AMP were initially normal in both groups and no change was seen in either group with
phosphorus deprivation. In the normal subjects, 1,25(
OH)2D levels rose progressively over the 96 h of the study (49 +/- 3 to 63 +/- 6 pg/ml, P less than 0.05), while mean circulating 1,25(
OH)2D in the patients with FHR did not change (34 +/- 3 to 29 +/- 3 pg/ml). The changes in individual plasma 1,25(
OH)2D levels correlated strongly with the change in individual nephrogenous
cyclic AMP measurements in the patients with FHR (r = +0.93), while no such correlation was observed in the normal subjects. These data demonstrate a defective renal response to
phosphorus deprivation in patients with FHR including a qualitatively abnormal response in 1,25(
OH)2D generation.