Cinacalcet as a First-Line Treatment in Neonatal Severe Hyperparathyroidism Secondary to Calcium Sensing Receptor (CaSR) Mutation

Introduction: Neonatal severe hyperparathyroidism (NSHPT) is a rare cause of neonatal hypercalcemia caused by a loss of function mutation in the calcium-sensing receptor (CaSR). Hypercalcemia in NSHPT can be life-threatening. Maintenance of serum calcium within a safe range is the primary goal of treatment through hydration, forced diuresis, and bisphosphonate treatment, nevertheless most cases require parathyroidectomy. We report a case with NSHPT diagnosed on the first day of life (DoL) and successfully treated with cinacalcet as the first-line treatment from the 2nd DoL up to the age of 18 months. Case Report: A full-term baby evaluated for weight loss at postnatal 14th hour and found to have hypercalcemia (14.4 mg/dL, reference range [RR]: 8.0–11.3). Despite hydration and diuresis, hypercalcemia persisted. Further evaluation revealed a parathyroid hormone (PTH) level of 1,493 pg/mL (RR: 15–65) and urine Ca/Cr of 0.09 mg/mg (RR: 0.03–0.81). Cinacalcet treatment was initiated on the 2nd DoL with the diagnosis of NSHPT due to hypocalciuric hypercalcemia and elevated PTH level. Ca levels decreased to normal levels on the 7th DoL. She was discharged from hospital at postnatal day 15 on cinacalcet treatment and still continued at 18 months of age. Sequencing of CaSR revealed a novel homozygous c.1836G>A (p.G613E) mutation in the patient, for which the parents and sister were heterozygous. Conclusion: This case represents the youngest age at cinacalcet initiation and the longest duration without parathyroidectomy in a homozygous NSHPT and demonstrates that cinacalcet is an effective first-line treatment in patients who are responsive to this treatment modality and allows avoiding/delay in surgical intervention in NSHPT.