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A case of X-linked hypophosphatemic rickets (XLH): complications and the therapeutic use of cinacalcet

H Raeder, Dept of clinical medicine, University of Bergen, Section for pediatrics, Bergen, 5021, Norway
R Bjerknes, Department of Pediatrics, Haukeland University hospital, Section for pediatrics, Dept of clinical medicine, University of Bergen, Bergen, Norway
N Shaw, Endocrinology, Birmingham Children's Hospital, Birmingham, United Kingdom
C Netelenbos, Department of Endocrinology, Academic Hospital Vrije Universiteit Amsterdam, Amsterdam, Netherlands

Correspondence: Helge Raeder, Email: helge.rader{at}uib.no

Abstract

In hypophosphatemic rickets there are both inherited and acquired forms, where X-linked dominant hypophosphatemic rickets (XLH) is the most prevalent genetic form and caused by mutations in the PHEX gene. XLH is associated with growth retardation and bone deformities.

The renal tubular cells have an important role in calcium and phosphate metabolism, where the 1alpha hydroxylase enzyme metabolises the conversion of 25 OH-Vitamin D to potent 1,25 (OH)2-Vitamin D, whereas the sodium-phosphate transporter control tubular phosphate reabsorption. The pathophysiological defect in XLH is speculated to cause an increase in a circulating phosphate regulating hormone termed phosphatonin (FGF23 is the primary phosphatonin candidate) which leads to inhibition of 1alpha hydroxylase, and simultaneously to inhibition of the sodium-phosphate transporter domain NPT2c leading to PTH-independent phosphaturia. Hence, current treatment of XLH is 1,25 (OH)2-Vitamin D or the Vitamin D analogue alfacalcidol and elementary phosphorus. Unfortunately, patients with XLH may develop nephrocalcinosis, secondary or tertiary hyperparathyroidism, and in some situations also hypertension and cardiovascular abnormalities.

We describe a patient with XLH, caused by a novel missense mutation in the PHEX gene, who on treatment with alfacalcidol and oral phosphate had normal growth and minimal bone deformities, but who subsequently developed moderate nephrocalcinosis, significant hyperparathyroidism, hypercalcemia, renal failure and hypertension. We also report the use of the calcimimetic drug cinacalcet in the successful treatment of hypercalcemia and hyperparathyroidism.