SAT217 Chronic Asymptomatic Hypoparathyroidism Due To Two Separate Single Nucleotide Heterozygous Mutations In The CaSR Gene

Abstract

Abstract Disclosure: M. Antony: None. S. Gundlapally: None. S. Storm: None. P. Russell: None. V. Verma: None. R. Kant: None. Introduction: The most common cause for acquired hypoparathyroidism is either post-surgical or autoimmune destruction of the parathyroid glands. The clinical presentation can range from an asymptomatic state to severe life-threatening symptoms that require intensive therapeutic management with intravenous and/or oral calcium, calcitriol and in some cases, recombinant parathyroid hormone therapy. Hypoparathyroidism secondary to CASR (calcium sensing gene receptor) gene mutation is an uncommon etiology that can also have a varied clinical presentation as above. Clinical Case: A 60-year-old Caucasian male with no significant past medical history was found to have chronic hypocalcemia. He denied experiencing symptoms such as numbness, tingling or cramping sensation around face, lips, or upper extremities. He denied a history of movement disorder or dental problems. He denied a history of neck surgeries or neck radiation exposure. He denied a family history of calcium disorders. He was on calcium carbonate/Vitamin D3 600 mg/400 I.U once daily. The first documented low corrected serum calcium was 6.9 mg/dl (8.6-10.0 mg/dl) in November of 2017. Since then, there have been multiple low corrected serum calcium levels ranging between 7 to 7.6 mg/dl. Patient underwent endocrinology work-up after withholding the above calcium/Vitamin D3 supplementation and it revealed a low corrected serum calcium of 7.6 mg/dl with an inappropriately normal serum PTH level of 37 pg/ml (15-65 pg/ml), normal vitamin D level of 45.1 ng/ml (> 30.0 ng/ml), normal serum phosphorus 3.8 mg/dl (2.5-4.5 mg/dl), and normal serum magnesium 1.8 mg/dl (1.6-2.6 mg/dl). The 24-hour urine calcium was 93 mg/24 hour with a corresponding 24-hour urine creatinine of 1836 mg (1040-2350 mg/24hour) and urine volume of 1625 ml. CASR gene analysis revealed two separate single nucleotide heterozygous mutations. The first mutation was at Exon 4/7, nucleotide position was c.614G>A and Amino Acid position was p.Arg205His. The second mutation was at Exon 7/7, nucleotide position was c.2546T>C and Amino Acid Position is p.lle849Thr. Due to lack of specific symptoms, patient was not initiated on specific therapies such as calcitriol or Natpara (recombinant PTH) and was advised to continue taking the daily calcium/vitamin D3 supplementation. He is being currently monitored every 4 to 6 months to assess for any clinical symptoms along with pertinent laboratory work-up. Conclusion: Hypoparathyroidism due to CASR gene mutation has a varied clinical presentation. One-third of cases do not develop any clinical symptoms, such as our patient and hence do not warrant any specific treatment other than periodic clinical and biochemical assessment. Presentation: Saturday, June 17, 2023