Homozygous loss-of-function mutations of the calcium-sensing receptor gene (CaSR) are associated with neonatal severe hyperparathyroidism (NSHPT), a life-threatening condition with a challenging treatment approach.
We report a 7-day-old-female infant who was admitted to our Pediatric Department due to poor sucking. On examination she was lethargic and hypotonic. Laboratory evaluation revealed extreme hypercalcemia of 23.54 mg/dL (N: 7.610.4) with normal albumin levels, low phosphorus concentration of 2.16 mg/dL (N: 4.06.5), and extremely high PTH of 568 pg/mL (N: 18.480.1). The biochemical findings indicated NSHPT. Treatment was initiated with hyperhydration and IV bisphosphonate and calcitonin for the first 24 hours, which reduced calcium levels to the normal range within days. Cinacalcet was thereafter initiated at a dose of 0.35 mg/kg per day with an increase up to 7.5 mg/kg per day. Skeletal survey revealed bone deformities of the femur with evidence of growth-plate injury and severe osteopenia. Molecular analysis of CaSR identified a novel homozygous mutation: c.281G>A (p.Gly94Glu). The parents are first cousins and were heterozygous ; the mother had had elevated PTH levels in the past that normalized with vitamin D therapy, and the paternal grandmother had undergone parathyroidectomy (PTX). Despite normal calcium levels, our patient's PTH remained elevated and there was progressive bone disease. Therefore, at 9 weeks of age, a total PTX with auto-transplantation of one gland in the thigh was performed. After PTX, the PTH levels decreased and hypocalcemia gradually evolved, necessitating initiation of oral calcium and alfacalcidol. This case report demonstrates the challenges of treating NSHPT and indicates that the therapeutic goal must be to reduce serum levels of both calcium and PTH, as elevated PTH by itself can cause severe bone deformities. Finally, because CaSR has specialized roles in the brain and bone cells, even with correction of serum calcium and PTH levels, these patients remain at risk for neurocognitive and skeletal defects.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology