Neonatal severe primary hyperparathyroidism (NSHPT) is a rare and life-threatening disorder caused by inactivating mutation in CASR gene, which encodes Ca-sensing receptor. NSHPT leads to severe neonatal hypercalcemia with inappropriately increased serum intact parathyroid hormone (iPTH) and decreased urinary Ca excretion. Hydration, forced diuresis, calcitonin, bisphosphonates and cinacalcet have been used to lower serum Ca prior to surgery. Total parathyroidectomy is the standard treatment but is challenging in neonatal period. We present a female infant who was born to consanguineous parents and presented at the age of 7 days with lethargy and respiratory distress. Chest radiograph revealed bell-shaped thoracic cage, multiple rib fractures and generalized osteopenia. Blood chemistries showed markedly elevated serum Ca at 24.8 mg/dL, P 2.1 mg/dL and iPTH 872 pg/mL. The fractional excretion of urinary Ca was relatively low at 2.6%. Severe neonatal hypercalcemia with findings of serum P, iPTH and urinary Ca levels led to the diagnosis of NSHPT. She was promptly treated with intravenous saline, furosemide, salmon calcitonin and bisphosphonates. However, serum Ca remained elevated at 11-15 mg/dL. Cinacalcet was then initiated with a maximum dose of 90 mg/m2/day without success. Therefore, total parathyroidectomy was undertaken at 2 months of age. Owing to the difficulty of performing parathyroidectomy in a small infant, intraoperative iPTH levels were monitored to ensure complete removal of parathyroid glands. The serum iPTH fell from the preoperative level of 755 to 26 pg/mL at 20 minutes after excision of 4 parathyroid glands. She developed hypocalcemia secondary to hypoparathyroidism 10 days after the operation. CASR mutation analysis identified a novel homozygous nonsense mutation, c.1660C>T (p.Arg554*). The mutation leads to a stop codon and is predicted to produce a shorter protein from 1088 to 554 amino acids. Her parents were cousins and had slightly elevated serum Ca and iPTH but low urinary Ca excretion. Each parent is likely to have the heterozygous mutation. However, the familial mutation test has not been performed.
Our findings demonstrated a novel p.Arg554* mutation as a cause of NSHPT which did not respond to the medications including cinacalcet. A mutation analysis could minimize an unnecessary prolonged period of medications.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology