ODP104 Isolated familial hypoparathyroidism with Tbx1 mutation in Korea

BACKGROUND: Non-surgical hypoparathyroidism due to lack of PTH secretion or action is uncommon disorder characterized by hypocalcemia and hyperphosphatemia. Familial hypoparathyroidism is classified into syndromic hypoparathyroidism, including DiGeorge syndrome and isolated familial hypoparathyroidism. Deletion of Tbx1 is the cause of DiGeorge syndrome characterized by hypoparathyroidism, immunodeficiency, and congenital heart disease. Most cases of isolated familial hypoparathyroidism are caused by GCM2, SOX3, CASR, Gα11, and PTH. Isolated familial hypoparathyroidism also can be caused by mutations in TBX1 genes(1). In this study, we also identified a splice-altering mutation in TBX1 (c.1009+1G. C), leading to skipping of exon 8 in an idiopathic hypoparathyroidism patient in Korea. CASE: A 35-year-old woman was referred to our hospital in March 2016 for hypocalcemia. It had been detected after recurrent abortion and seizure during exercise. Her second older brother was diagnosed as idiopathic hypoparathyroidism with no abnormalities in the TUPLE1 FISH test and chromosome test eight years ago. Initial laboratory studies showed low corrected calcium (7.4 mg/dL, normal range: 8.5-10.5), hyperphosphatemia (4.7 mg/dL, normal range: 2.5-4.1), inappropriately normal parathyroid hormone (18.4 pg/mL, normal range: 15-65), corresponded to hypoparathyroidism. A brain computed tomography showed bilateral globus pallidi calcification. She had no history of renal stones or cataracts. She did not show congenital anomaly including cleft palate, facial dysmorphism, conotruncal heart defects, and immunodeficiency, and neither did her brother. Molecular diagnoses were analyzed by whole-exome sequencing, identifying the heterozygous TBX1 mutation (c.1009+2T/A). She was treated with conventional therapy such as calcium and calcitriol. The patient gave birth 18 months after referring to our hospital, and the child did not show any abnormalities in calcium or phosphorus. During a follow-up of 6 years, the patient had no additional symptoms related to hypocalcemia with the lower normal range of calcium and normal phosphorous. CONCLUSION: We identified a rare heterozygous TBX1 mutation in a patient with isolated familial hypoparathyroidism in Korea. References1. Li D, Gordon CT, Oufadem M, et al. Heterozygous Mutations in TBX1 as a Cause of Isolated Hypoparathyroidism. The Journal of Clinical Endocrinology & Metabolism.2018;103(11): 4023-4032. Presentation: No date and time listed