Management of Severe Neonatal Hyperparathyroidism due to a Novel Homozygous CaSR Mutation - הכינוס השנתי של החברה הישראלית לפדיאטריה קלינית

אמיר הכהן סולוביץ ¹ Yardena Tenenbaum-Rakover ² Ronen Spiegel ¹ Jeffrey Weinberger ³ David Gillis ⁴ Gershon Goor Zamir ⁵ Michael A Levine ⁶ Tal Almagor ^1,2

¹Pediatric Department B, Ha'emek Medical Center, ישראל
²Pediatric Endocrine Institute, Ha'emek Medical Center, ישראל
³Department of Otolaryngology and Neck Surgery, Hadassah – Hebrew University Medical Center, ישראל
⁴Department of Pediatrics, Hadassah – Hebrew University Medical Center, ישראל
⁵Pediatric Intensive Care Unit, Ha'emek Medical Center, ישראל
⁶Center for Bone Health, Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, ארצות הברית

Background: 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.

Case description: A 7-day-old-female infant admitted to our Pediatric Department due to feeding difficulties, lethargy and hypotonicity. Laboratory evaluation revealed:Extreme hypercalcemia of 23.54 mg/dL (N: 7.6–10.4),Low phosphorus concentration of 2.16 mg/dL (N: 4.0–6.5),Extremely high PTH of 568 pg/mL (N: 18.4–80.1).These findings suggested Neonatal Severe Hyperparathyroidism (NSHPT) due to CaSR mutation. Skeletal survey revealed bone deformities with evidence of growth-plate injury and severe osteopenia. Molecular analysis of CaSR identified a novel homozygous mutation: c.281G>A(p.Gly94Glu).

Calcium and PTH levels over 70 days

Treatment: Treatment was initiated with aggressive hydration, IV bisphosphonate and calcitonin for the first 24 hours. This treatment reduced calcium levels to normal range within days. Following treatment with Cinacalcet was initiated at a dose of 0.35 mg/kg per day with an increase up to 7.5 mg/kg per day.Despite normal calcium levels, PTH remained elevated and there was progressive bone disease.

At 9 weeks of age, a total PTX with auto-transplantation was performed. After PTX, PTH levels decreased and hypocalcemia gradually evolved. This necessitated initiation of oral Ca and alfacalcidol.

Discussion and Conclusion: 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. Cinacalcet treatment should be considered as initial treatment, BUT if it is ineffective, a definitive surgery should not be delayed.