Bone Abstracts

Background: A 5-month-old girl was referred to our unit after a systemic screening for hip dislocation by X-rays revealed bilateral femoral bowing. She was the first child of healthy non-consanguineous parents, and her family history was unremarkable. Her parents had a normal physical examination, and normal laboratory findings. At presentation, her height was 64.0 cm (Z-score: 0.0) with a regular height velocity. Weight was 7.4 kg (Z-score: 1.0). On physical examination, there was bilateral bowing of the femurs. The remaining examination was unremarkable.

Presenting problem: Laboratory investigations revealed hypercalcemia (total calcium 3.20 mmol/l), phosphatemia at lower limit (1.6 mmol/l), normal alkaline phosphatase level (643 IU/l), inappropriate level of intact PTH (85 pg/ml), and urinary calcium:creatinine ratio at upper limit (1.08 mmol/mmol). Serum 25-hydroxyvitamin D (25OH D) level was normal (23 ng/ml). A skeletal survey revealed bilateral femoral bowing without other bone abnormalities. Calcium-sensing receptor (CaSR) gene analysis found combined heterozygote mutations with a missense mutation resulting in amino-acid N592S substitution in the extracellular domain and a R648X nonsense mutation.

Clinical management: Intravenous disodium pamidronate (two infusions of 0.5 and 1.0 mg/kg at months 6 and 7 respectively) was administrated to control the excess of bone resorption and hypercalcemia. Tolerance was good. Calciuria decreased under treatment. Cholecalciferol was associated.

Discussion: We report here a new case of neonatal hypocalciuric hypercalcemia responsible for bone deformity with combined mutations of the CaSR gene. Inactivating mutations of the CaSR gene usually cause familial hypocalciuric hypercalcemia, an autosomal dominant disorder characterized by hypercalcemia, inappropriately high PTH levels, and low urinary calcium excretion. Various managements have been proposed. Because of the bone presentation, instead of reduction of calcium intake and cholecalciferol administration, we indicated biphosphonate treatment in order to reduce hypercalcemia and the consequences of chronic hyperparathyroidism. Calcemia remained controlled and calciuria was reduced, indicating reduction of the bone turn-over. Like in other cases of hyperparathyroidism, the use of biphosphonates seemed to us logical as transient treatment in cases of CaSR mutations associated with bone lesions. Use of calcimimetics also should be further considered when the mutations potentially affect CaSR binding.