Work

Management of Neonatal Severe Hyperparathyroidism Due to Homozygous CASR Mutation: Challenges and Literature Insights

Year: 2025

Type: article

Abstract: Introduction: Neonatal severe hyperparathyroidism (NSHPT) is a rare but life-threatening disorder caused by inactivating variants in the calcium-sensing receptor (CaSR), resulting in severe hypercalcemia during the neonatal period. Infants with NSHPT may present with severe hypercalcemia, hyperparathyroidism, growth retardation, and respiratory distress. If untreated, NSHPT can lead to life-threatening complications. Due to its rarity, few cases have been reported in the literature. Case presentation: A 4-day-old girl presented with jaundice, weight loss, and hypercalcemia (16 mg/dL). On physical examination, she appeared dehydrated, hypotonic, and had facial dysmorphisms. Laboratory results revealed markedly elevated parathyroid hormone (PTH) levels (1769 pg/mL) and low urinary calcium excretion. Despite initial treatment with hydration and furosemide, her hypercalcemia persisted. Cinacalcet was started but failed to control calcium levels, leading to the need for a subtotal parathyroidectomy at 2.5 months of age. Genetic testing identified a homozygous mutation in the CASR gene (p.Met741LeufsTer24). Postoperatively, the patient developed hypocalcemia due to hungry bone syndrome and later experienced recurrent hypercalcemia, which was managed with pamidronate followed by calcitriol. At 21 months of age, she remains normocalcemic on daily calcitriol. Conclusion: This case highlights the challenges in managing NSHPT, especially in cases resistant to medical treatment. Subtotal parathyroidectomy proved essential for controlling hypercalcemia. Continued documentation of NSHPT cases will help improve treatment strategies and outcomes for this rare condition.

Source: Molecular Syndromology

DOI: 10.1159/000543911