PLK was2 2 SD for weight and height, and the patient developed psychomotor retardation mainly in motor acquisition. At age 2 years, treatment with bisphosphonates was initiated. The patient benefited frompamidronate infusion every 4 months between December 2001 and November 2005. Supplementation with vitamin D and sodium phosphate was also initiated. Calcium decreased to 3 mmol/L, PTH decreased to 10 pmol/L. The other laboratory values changed as follows: phosphate 0.9 mmol/L, 25 OH cholecalciferol 102 nmol/L, urinary calcium/creatinine ratio 0.1. Bone turnover markers: urinary molar fraction deoxypridinoline/ creatinine 71, serum osteocalcin: 51 mg/ L, alkaline phosphatase 230U/L. The BMD of the spine L2 to L4 showed an improved z score at 1.3. Finally, nephrocalcinosis on the renal ultrasound decreased. The patient did much better, and we observed an improvement of psychomotordelay and staturoponderal growth. At age 6 years, a trial with cinacalcet was started with a first dose of 30 mg, which was increased to 90 mg and 60 mg a day on RAAS System alternating days. With this treatment, calcium level decreased to 2.6 mmol/L, and PTH lowered to 5 pmol/L.
The other laboratory results enzalutamide changed as follows: phosphate 1.14 mmol/L, 25 OH cholecalciferol 76 nmol/L, urinary calcium/creatinine ratio 0.2, bone turnover markers: serum osteocalcin 80 mg/L, alkaline phosphatase 214 U/L. Under cinacalcet, the patient growth continued to follow the 1 SD, and no other secondary effects were observed. In 2010, calcium increased to 2.8 mmol/L and PTH to 5.5 mmol/L, and we increased cinacalcet to 90 mg per day with a good results, calcium decreased to 2.6 mmol/L and PTH to 4.6 pmol/L. These examinations were done at the university hospital of Limoges by Drs Sturtz and Magdelaine. The molecular biology demonstrated a homozygous mutation in the third exon of the CasR gene. This mutation has never been described before and is characterized by the replacement of an arginine by a histidine in position 69 in the extracellular domain of the protein. Each parent carries the mutation in a heterozygous state. In vitro activity of the mutation is currently being tested. DISCUSSION Although surgery is currently the only curative treatment for NPHT, our patient had residual parathyroid tissue. As an alternative, we started treatment with bisphosphonates. Under bisphosphonates, as expected, we observed an improvement of altretamine calcium level. The BMD normalized and the bone turnover markers improved.
Statural growth increased, and the patients psychomotor skills improved. We also noticed an unexpected diminution of PTH from 20 pmol/L to 10 pmol/L, which was not completely understood. Usually, bisphosphonates induce a fall in blood calcemia and an additional increase in PTH. This unexpected fall in PTH level might represent a natural evolution of the disease.7 It might also result from a different bone contrary metabolism under treatment, but the mechanism remains unclear. CaSR is expressed in the bone, but no link between bone CaSR and parathyroid gland regulation has beendescribed. Fibroblast growth factor 23 is also secreted in the bone and is known to decrease PTH secretion, however, recent articles showed that pamidronate induces a fall in fibroblast growth factor 23 secretion.