Familial adult onset X-linked hypophosphataemic osteomalacia (report of a family; clinical and experimental studies)

From four patients (a great-grandmother, grandmother, her daughter and her grandson) suffering from a very severe form of familial X-linked hypophosphataemic osteomalacia (XLH), belonging to a 23-number-kindred of five generations, the youngest patient a 24-year-old man with an adult onset XLH was treated with phosphate and calcitriol for two years. Phosphate was given in increasing doses (500-6000 mg elemental phosphate) by mouth for a relatively short-term period and calcitriol in high doses per os combined with intermittent intravenous administration. Long-term treatment consisted of daily three grams of phosphate and 1.25 micrograms calcitriol by mouth combined with daily 2 micrograms calcitriol intravenously for one week every month. Dramatic clinical improvement occurred accompanied with definite radiological and scintigraphical changes. Serum phosphate increased from 0.525 +/- 0.478 mmol/l to 1.054 +/- 0.041 mmol/l (p < 0.001) in response to 3000 mg phosphate. A close correlation (r = 0.69) was found between serum phosphate and urinary phosphate excretions (p < 0.001) and an inverse correlation (r = -0.31) was found between serum phosphate and tubular reabsorption of phosphate (p < 0.01). Serum and urinary calcium values, parathormone as well as renal functions did not change. Administration of high doses of phosphate seemed to be an effective and probably safe form of treatment in XLH provided that development of hyperparathyroidism is prevented by the coadministration of high doses of calcitriol.