Related Experiment Videos
Hereditary hypophosphatemic rickets with hypercalciuria
Insights
This study identifies a new hereditary syndrome causing hypophosphatemic rickets and hypercalciuria. Phosphate supplementation reversed most symptoms, suggesting a renal phosphate leak as the primary defect.
Area of Science:
- Endocrinology
- Nephrology
- Genetics
Background:
- Hereditary hypophosphatemic rickets and hypercalciuria is a rare condition.
- Understanding its genetic basis and pathophysiology is crucial for effective treatment.
Purpose of the Study:
- To characterize a novel hereditary syndrome presenting with hypophosphatemic rickets and hypercalciuria.
- To investigate the underlying mechanisms and therapeutic responses.
Main Methods:
- Clinical evaluation of six affected individuals from one family.
- Biochemical analyses including serum calcium, phosphate, 1,25-dihydroxyvitamin D, and parathyroid hormone levels.
- Measurement of renal phosphate clearance (TmP/GFR) and urinary calcium excretion.
Main Results:
- Patients exhibited rickets, short stature, increased renal phosphate clearance, hypercalciuria, and elevated 1,25-dihydroxyvitamin D.
- Serum calcium was normal, with suppressed parathyroid function.
- Phosphate supplementation normalized clinical and biochemical findings, except for decreased TmP/GFR.
Conclusions:
- The syndrome is characterized by a renal phosphate leak leading to hypophosphatemia and secondary hypercalciuria.
- Elevated 1,25-dihydroxyvitamin D plays a key role in calcium absorption and parathyroid suppression.
- Phosphate is critical in regulating 1,25-dihydroxyvitamin D production in humans.
Abstract:
We studied a new hereditary syndrome of hypophosphatemic rickets and hypercalciuria in six affected members of one kindred. In all patients, the manifestations of disease began in early childhood. The characteristic features are rickets, short stature, increased renal phosphate clearance (the ratio between the maximal tubular reabsorption rate for phosphorus and the glomerular filtration rate [TmP/GFR] is 2 to 4 S.D. below the age-related mean), hypercalciuria (8.6 mg of urinary calcium per kilogram of body weight per 24 hours vs. the upper normal value of 4.0), normal serum calcium levels, increased gastrointestinal absorption of calcium and phosphorus, an elevated serum concentration of 1,25-dihydroxyvitamin D (390 +/- 99 pg per milliliter vs. the upper normal value of 110), and suppressed parathyroid function (an immunoreactive parathyroid hormone level of 0.33 +/- 0.1 ng per milliliter and a cyclic AMP level of 1.39 +/- 0.12 nmol per deciliter of glomerular filtrate vs. the lower normal values of 0.3 and 1.5, respectively). Long-term phosphate supplementation as the sole therapy resulted in reversal of all clinical and biochemical abnormalities except the decreased TmP/GFR. We propose that the pivotal defect in this syndrome is a renal phosphate leak resulting in hypophosphatemia with an appropriate elevation of 1,25-dihydroxyvitamin D levels, which causes increased calcium absorption, parathyroid suppression, and hypercalciuria. This syndrome may represent one end of a spectrum of hereditary absorptive hypercalciuria. Our observations support the importance of phosphate as a mediator in controlling 1,25-dihydroxyvitamin D production in human beings.