X-Linked Hypophosphatemic Rickets: Report of a Novel PHEX Mutation and Cinacalcet as Adjuvant Therapy in the Mineral Metabolism Control.

X-linked hypophosphatemic rickets (XLH) is a rare disease caused by a mutation in the PHEX gene, located on the X chromosome. This gene encodes the phosphate regulating endopeptidase, and its inactivation leads to increased levels of circulating phosphatonins responsible for renal phosphate loss. The treatment of XLH is still carried out with long-term administration of phosphate and calcitriol, which can be complicated by hyperparathyroidism, nephrocalcinosis, renal failure and hypertension. We describe the case of a four-decades follow-up patient with XLH. When she was diagnosed, at 19, due to bone pain and deformities, she was put on therapy with phosphorus and cholecalciferol. Despite the clinical improvement, serum phosphorus remained difficult to control. At the age of 44, she developed tertiary hyperparathyroidism and was submitted to parathyroidectomy. Five years later, parathyroid hyperfunction recurred. This time, cinacalcet was started, 30 mg alternating with 60 mg/day. Currently, she is 59 years-old and remains with controlled mineral metabolism. The genetic study of this patient revealed a nonsense heterozygous mutation (c.501G> A) in PHEX gene that was not previously described. In this case, the off-label use of cinacalcet resulted in the normalization of serum PTH and phosphorus levels, eliminated recurrent secondary hyperparathyroidism, which aggravates the bone fragility inherent to XLH and prevented a new parathyroidectomy. This report also adds important information to the genetic basis of XLH with the identification of a new nonsense mutation of the PHEX gene.