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.

A 4-year-old girl presented with severe clinical and radiological rickets, and alopecia since the age of 1 year. Laboratory studies revealed: hypocalcaemia, hypophosphataemia, secondary hyperparathyroidism, abnormally low intestinal calcium absorption, and markedly elevated circulating 1,25(OH)2D3 levels. A normal calcaemic response to parathyroid extract was obtained. Treatment attempts with vitamin D2, 1 alpha (OH)D3 and 1,25(OH)2D3 were totally ineffective. Intestinal resistance to the action of 1,25(OH)2D3 appeared well established in this case. Refractoriness of bone to this hormone seems less certain. From this new entity of 'Vitamin D resistant rickets due to end organ unresponsiveness', six cases have been hitherto reported in the literature. However, only two have enough resemblance to our case, to constitute a distinct and well defined nosologic subunit. The molecular basis of this disorder(s) remains to be elucidated.

Peripheral and bone marrow eosinophils were determined in a group of patients on chronic hemodialysis and in predialysis uremics. Healthy subjects were taken as controls. Increased number of eosinophils in bone marrow were found in the predialysis uremic group and this finding was even more accentuated in the dialyzed patients. Marrow eosinophilia correlated linearly with serum creatinine levels in the predialysis group. The peripheral eosinophil count was normal in the uremic group and in part of the hemodialysis group. Marked and progressive peripheral eosinophilia was evident in a distinct subgroup of the dialysis patients. Marrow eosinophilia seems to be part of the uremic syndrome. The possible nature of the factor(s) involved in the derangement of eosinophil homeostasis is discussed.

The treatment of X-linked hypophosphatemia (XLH) consists of phosphate and vitamin D₃ derivatives. Transient hypercalciuria and hypercalcemia are well-known signs of vitamin D intoxication. Despite urinary calcium excretion control, the danger of nephrocalcinosis in treated patients has been emphasized. It has recently been suggested that hyperoxaluria might be a causative factor of nephrocalcinosis other than calcium in phosphate-treated XLH patients. We measured urinary oxalate and phosphate excretion in 12 patients with the syndrome of hereditary hypophosphatemic rickets with hypercalciuria (HHRH) receiving only oral phosphates and in 5 XLH patients receiving both oral phosphates and vitamin D. No correlation was found between the dosage of phosphate supplements or urinary phosphate excretion and urinary oxalate excretion, in either group of patients. Nephrocalcinosis, presenting as hyperechogenicity of the medullary pyramids, was found in 2 of the 5 XLH patients and only in 2 HHRH patients who had been treated with excessive doses of vitamin D₂ and calcium, prior to the true diagnosis being established. We conclude: (1) hyperoxaluria is not a cause of nephrocalcinosis in phosphate-treated patients with hereditary hypophosphatemic rickets; (2) prolonged phosphate treatment alone does not induce nephrocalcinosis in HHRH patients, and (3) we believe that in XLH patients, nephrocalcinosis is essentially due to vitamin D overdosage at some stage, or noncompliance in phosphate intake, leading to repeated undetected hypercalciuric periods.