Neonatal severe hyperparathyroidism with inactivating calcium sensing receptor (CaSR) mutation (p.I81K)

Neonatal severe hyperparathyroidism (NSHPT) is a rare condition characterized by inactivating mutations in the calcium-sensing receptor (CaSR) gene, leading to significant hypercalcemia and related complications.

We present a case of a six-day-old male infant with weakness, jaundice, and hypotonia, later diagnosed with NSHPT due to a known homozygous CaSR mutation (c.242T>A; p.I81K). Initial laboratory findings revealed markedly elevated serum calcium levels and high parathyroid hormone levels which were compatible with primary hyperparathyroidism. After initial management, bisphosphonates were administered, resulting in the patient remaining normocalcemic for 11 months, although hyperparathyroidism persisted. Then, due to the ongoing hyperparathyroidism, cinacalcet was added and continued for nine months. Finally, a total parathyroidectomy was performed. Postoperatively, the patient developed hypoparathyroidism, necessitating long-term supplementation with calcium and calcitriol. By the last follow-up at 3 years, the patient exhibited normal growth parameters and no neurodevelopmental deficits.

This case underscores the importance of early diagnosis and intervention in NSHPT and highlights the critical role of medical treatment, surgical management and long-term follow-up in optimising patient outcomes. Continued research is essential to enhance understanding and treatment strategies for NSHPT.