To evaluate the effect of early treatment on calcium metabolism and growth of infants with X-linked hypophosphataemic rickets (XLH), we enrolled eight infants (one boy) with XLH in a prospective study before and during combined treatment with 40 60 mg/kg per day phosphate and 20-40 ng/kg per day 1,25(OH)2D3 (calcitriol). The duration of treatment ranged from 12 to 68 months (median 27 months). We measured the height and several indices of calcium and bone metabolism before and at intervals of 6 weeks to 3 months thereafter during treatment. The diagnosis XLH was established between the age of 3 to 12 weeks by the detection of elevated alkaline phosphatase activities (n = 8) and urinary hydroxyproline (n = 7), whereas only five patients had also hypophosphataemia. Six of seven untreated patients had decreased 1,25(OH)2 vitamin D levels in serum. During treatment alkaline phosphatase and hydroxyproline decreased to normal or slightly elevated levels, whereas serum phosphate remained below the normal range. Several patients treated with more than 40-50 mg/kg per day phosphate developed secondary hyperparathyroidism. One patient receiving a low dose of 20 ng/kg per day calcitriol had prolonged radiological and biochemical signs of rickets and growth delay. The other patients presented with no or only slightly transient signs of rickets. Three patients developed moderate nephrocalcinosis. The statural growth rate decreased slightly below 2 SDs without a further decrease in two patients and remained within the normal range in the other patients. Only four patients developed moderate leg deformities.
Conclusions: Early treatment with calcitriol at a daily dose of at least 30-40 ng/kg and phosphate at a daily dose of maximal 40-50 mg/kg improves mineral metabolism and seems to obviate severe growth delay and leg deformities.