الكاتب: Multiple References

A new syndrome, H.H.R.H. was recently described in 8 members of one kindred. Studies of 49 additional asymptomatic members of this kindred revealed: 29 normal subjects (N.), while 20 others had hypercalciuria (I.H.) with no evidence of bone disease. The following indices distinguished the 3 different groups: 24h urinary calcium creatinine ratio (C&r.) 0.43 * 0.14 (mean 2 SD) in H.H.R.H., 0.34 ? 0.07 in I.H., and 0.14 + 0.05 in N. Serum phosphorus (Pi) and TmP/GFR as determined by age related means and expressed in SD units were -4.31 + 2.38 and -3.0 ? 1.24 in H.H.R.H., -1.11 f 0.98 and -1.13 ? 0.57 for I.H., +O.Ol ? 0.98 and +0.21 + 0.94 for N. Serum levels of 1.25(OH)*D were 303 + 208 pg/ml, 145 ? 99 and 84 2 36, in H.H.R.H., I.H. and N., respectively. Urinary CAMP excretion in H.H.R.H., I.H. and N. was 1.66 2 0.73, 2.69 -t- 1.05 and 3.28 ? 0.96 nmol/lOO ml.GF. respectively. A significant negative linear correlation was found between TmP/GFR, serum 1.25(OH)2D levels and urinary C&r in all subjects. We propose that the pivotal genetic defect in this kindred is a renal Pi leak resulting in hypophosphatemia and an appropriate elevation of 1.25(OH),D levels, which causes increased Ca absorption parathyroid suppression and hypercalciuria. We conclude 1. This kindred represents a new hereditary syndrome in which the affected site in the kidney is different from the known hypophosphatemic syndromes. 2. Pi is an important mediator in controlling 1.25(OH)2D in human. 3. The pathophysiological sequence operating in our I.H. subjects and H.H.R.H. patients is identical. 4. Quantitatively the abnormalities in I.H. are milder and the biochemical parameters are in between the values of H.H.R.H. and normals. 5. For the first time, the concept of idiopathic hypercalciuria as an expression of a specific inherited renal defect, is clearly illustrated.