MON-765 A Rare Case of Primary Hyperparathyroidism due to a New Variant of Glial Cells Missing 2 (GCM2) Gene Mutation

Abstract Disclosure: M. Tang: None. S. Carlson: None. S. Meng: None. Primary Hyperparathyroidism (PHPT) is a relatively common disorder that preferentially affects older women. Most PHPT cases are sporadic diseases, but rarely patients are associated with genetic abnormality. Clinical presentations vary from asymptomatic hypercalcemia to renal failure, kidney stones, and osteoporosis. We present a rare case of PHPT due to new variant of GCM2 mutation in a 27-year-old Hispanic female that was discovered after fractures. The patient presented to an outside hospital in September 2023 for a left distal femur fracture after a fall and was found to have lytic pelvic lesions on imaging. Her history was notable for polyuria and polydipsia, two occasions of kidney stones, and several falls over the past few years. The patient reported no maternal family history of parathyroid disease, hypercalcemia, or kidney stones, but paternal family history is unknown. After her third fall in May of 2023, further workup in August of 2023 showed a parathyroid hormone (PTH) level of 1027 pg/mL and calcium of 13.7 mg/dL. PHPT was diagnosed and parathyroidectomy was planned, but she was brought to the emergency room after an unexpected fall with fracture. She was given cinacalcet 30 mg daily and a dose of zoledronic acid, then underwent an open reduction and internal fixation with bone biopsy that showed findings consistent with a brown tumor. She was later transferred to our hospital for a higher level of care. Her calcium was 12.7 mg/dL, PTH 1,199 pg/mL, 25-OH vitamin D 9 ng/mL, phosphorus 1.1 mg/dL, and urine calcium 422 mg/24 hours. CT pelvis showed multilobulated lytic lesions within the left iliac bone and MRI of the left hip revealed a large expansile lesion in the left ilium with cortical erosion. A parathyroid SPECT/CT fusion scan confirmed a right inferior parathyroid adenoma, and she underwent right parathyroidectomy. Surgical pathology showed hypercellular parathyroid. Her hospital course was complicated by hungry bone syndrome requiring IV calcium, but the patient was eventually discharged on oral calcium and vitamin D in stable condition. Genetic testing was pursued. She was found to have a c.1109C>T (p.T370M) mutation in the GCM2 gene with 2 variants of uncertain significance in the BRCA2 gene. GCM2 is a nuclear transcription factor required for parathyroid gland organogenesis. Depending on the pathogenic mutation of this gene causing gain-of function or loss-of function, it can lead to sporadic familiar PHPT or hypoparathyroidism. To our knowledge, this is the first case of PHPT that is caused by the c.1109C>T (p.T370M) mutation in the GCM2 gene. We are unsure of the significance of the associated two new variants of the BRCA2 gene. In summary, awareness of this rare form of PHPT will lead to earlier diagnosis and intervention to prevent adverse outcomes. Presentation: Monday, July 14, 2025