Renal phosphate wasting disorders: clinical features and pathogenesis☆
Section snippets
XLH
XLH is a relatively common cause of rickets, with a prevalence of approximately 1 in 20,000. It is inherited in an X-linked dominant manner, with no evidence of a gene dosage effect, imprinting, or genetic anticipation.2 The disease is highly penetrant but has a wide range of expressivity.3 In other words, those carrying the mutation are likely to have the disease, but the severity of disease and specific clinical manifestations are variable, even among members of the same family.
Hyp mice and the phex gene
A murine model known as Hyp has been essential to our understanding of hypophosphatemic rickets. The Hyp mouse is characterized by renal phosphate wasting, growth retardation, and impaired bone mineralization.14 Corresponding to the inappropriately normal calcitriol levels in humans with XLH, 25-hydroxyvitamin D-1 α-hydroxylase activity in the Hyp mouse is inappropriately low for the level of hypophosphatemia.15 Hyp mice also have a primary osteoblast defect.16
To evaluate whether the phosphate
Treatment
Treatment of XLH and ADHR is similar, although no data exist on optimal treatment for ADHR.60 High doses of calcitriol are combined with high-dose phosphate supplementation until growth is complete. To minimize diarrhea and gastrointestinal upset from the phosphate, the dose should be increased gradually. Serum calcium, phosphorus, creatinine, and urine calcium and creatinine are monitored to allow titration of the calcitriol and phosphate dosage. It is not usually possible to normalize serum
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Supported by National Institutes of Health grants R01AR42228, R01DK063934, and K24-AR02095.