title: A case of X-linked hypophosphatemic rickets: complications and the therapeutic use of cinacalcet.
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 phosphate-regulating endopeptidase (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 metabolizes the conversion of 25 (OH)-vitamin D to potent 1,25 (OH)2-vitamin D, whereas the sodium-phosphate transporter controls tubular phosphate reabsorption. The pathophysiological defect in XLH is speculated to cause an increase in a circulating phosphate regulating hormone termed phosphatonin (fibroblast growth factor 23 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 parathyroid hormone-independent phosphaturia. Hence, current treatment of XLH is 1,25 (OH)2-vitamin D or the vitamin D analog 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.
authors.affiliation: Section for Pediatrics, Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. helge.rader@uib.no
authors.forename: Helge
authors.initials: H
authors.lastname: Raeder
authors.forename: Nick
authors.initials: N
authors.lastname: Shaw
authors.forename: Coen
authors.initials: C
authors.lastname: Netelenbos
authors.forename: Robert
authors.initials: R
authors.lastname: Bjerknes
mesh_terms: D000284:Administration, Oral; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000069449:Cinacalcet; D053098:Familial Hypophosphatemic Rickets / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D040181:Genetic Diseases, X-Linked; D006801:Humans; D006887:Hydroxycholecalciferols / Q000009:adverse effects / Q000627:therapeutic use; D006934:Hypercalcemia / Q000139:chemically induced* / Q000188:drug therapy*; D006961:Hyperparathyroidism / Q000139:chemically induced* / Q000188:drug therapy*; D006973:Hypertension / Q000139:chemically induced; D007223:Infant; D020125:Mutation, Missense; D009281:Naphthalenes / Q000627:therapeutic use*; D009397:Nephrocalcinosis / Q000139:chemically induced; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics; D010710:Phosphates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000139:chemically induced
chemical_list: D050071:Bone Density Conservation Agents; D006887:Hydroxycholecalciferols; D009281:Naphthalenes; D010710:Phosphates; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human; D000069449:Cinacalcet; C008088:alfacalcidol