SAT-769 Neonatal Hyperparathyroidism and Skeletal Dysplasia: A Case of Dual Molecular Diagnosis?

Abstract Disclosure: J. Limonta: None. G. Rivera Rodriguez: None. A. Diaz: None. C. Bustamante Escobar: None. A. Carrillo: None. A. Granados: None. This case highlights a rare presentation of a newborn with two genetic mutations affecting bone/calcium metabolism: CASR and KIF22, leading to complex metabolic and skeletal anomalies. The CASR mutation, associated with hyperparathyroidism and the KIF22 mutation associated with skeletal dysplasia and fractures. A newborn female was admitted to the NICU for respiratory distress, mild hypercalcemia and skeletal abnormalities. She was full term and developed respiratory distress requiring CPAP. She received feedings via an oro-gastric tube. Initial labs revealed a ionized calcium of 1.36 mmol/L, total calcium 11.8 mg/dL, phosphorus 4.3 mg/dl, iPTH 727 pg/mL, alkaline phosphatase (AP) 828 IU/L, 25 OH vitamin D of 41 ng/mL, and urinary Ca/Cr ratio 0.3 (neonate ref range 0.9-2.2). Imaging revealed diffuse osteopenia with skeletal abnormalities, including a bell-shaped thorax, gracile ribs, irregular costochondral junctions, periosteal reactions, and dysplastic versus healing non-displaced fractures. Brain CT showed wide cranial sutures without fractures. Patient was started on low calcium formula (Calcilo). Genetic testing reported a mutation in the gene CASR with the variant c.652 T>C p. (Y218H), heterozygous, classified as likely a pathogenic variant and KIF22 with the variant c.707 C>T p. (A236V), heterozygous, classified as a variant of unknown significance. Calcium improved to 9.6 mg/dl but iPTH and ALP continued to rise (1180 pg/ml and 1345 IU/L respectively). The patient was started on cinacalcet with the purpose of decreasing the iPTH, considering the severity of the bone findings. Despite treatment, she continued with persistent hyperparathyroidism (iPTH 1,546 pg/mL) and markedly elevated ALP (1,562 IU/L). Vi) and improved calcium of 8.9mg/dl. Upon follow up, her levels of 25 OH vitamin D were borderline low (/mL) and she was started on vitamin D3 400 IU daily. Patient required phosphorus replacement for a short period of time due to mild hypophosphatemia and high iPTH (phosphorus of 3.2 mg/dl). She was weaned from the oxygen and a gastric tube was placed due to feeding difficulties. Laboratory evaluations done prior to discharge showed a normal total calcium of 9.6 mg/dL, elevated iCal 1.36 mmol/L, iPTH 21.2, and phosphorus 4.4 mg/dl. The infant was discharged home on a low calcium formula, cinacalcet 4 mg PO BID, and vitamin D3 400 IU daily. The skeletal abnormalities observed, including fractures and osteopenia, was a consequence of the KIF22 mutation. Hypocalciuric hypercalcemia was secondary by the CASR mutations. The significant elevation of iPTH and ALP are likely secondary to the influence of these two mutations, since in isolation, no one is expected to produce these findings. This case illustrates how these two mutations resulted in a specific and unique clinical scenario. A deep understanding of the pathophysiology was essential to navigate this case. Presentation: Saturday, July 12, 2025