SAT-739 Case Report: Autosomal Dominant Hypocalcemia Type 2 In A 43-year-old Male Presenting At A Tertiary Canadian Medical Center

Abstract Disclosure: M.H. Alabdely: None. A.A. Khan: None. Background: Autosomal dominant hypocalcemia (ADH) type 1 and type 2 are rare disorders caused by gain-of-function variants that activate the calcium sensing receptor (CASR) gene, leading to ADH type 1, or its signaling protein Guanine nucleotide-binding protein subunit alpha-11 (GNA11), resulting in ADH type 2. These disorders are inherited in an autosomal dominant pattern and are characterized by hypoparathyroidism, manifesting as hypocalcemia, inappropriately low serum parathyroid hormone (PTH) concentrations and hypercalciuria due to enhanced sensitivity of the CaSR to extracellular calcium concentrations. Clinical features range from asymptomatic to severe. Treatment with calcium and active vitamin D can exacerbate hypercalciuria and nephrocalcinosis. Alternative treatment options that have been used in patients with ADH1 include recombinant human PTH or calcilytic therapy. Here, we describe a male patient with ADH2 harboring a novel GNA11 variant, evaluated at our tertiary center in Canada.Case summary:A 43-year-old male experienced intermittent numbness in hands for 3 years prior to presentation; in association with exercise. Other manifestations include bronchospasm and laryngospasm triggered by wrestling or climbing 2-3 flights of stairs, over the past 15 years. He had no peri oral numbness, muscle spasm, seizures, arrhythmias, brain fog, kidney stones, fractures or osteoporosis. Additionally, he had no clinical features features suggestive of genetic or autoimmune disorders resulting in hypoparathyroidism. There was no history of neck surgery or a family history of endocrine or autoimmune disease. In April 2024, he was incidentally found to have low calcium levels. By July 2024, he was found to have low PTH levels as well as persistently low calcium levels. Medical examination was unremarkable and Chvostek’s sign was negative. Laboratory tests revealed low corrected calcium (1.98 mmol/L, NR: 2.15-2.60), and low or inappropriately normal PTH (2.2 pmol/L, NR:1.6-9.3) on two occasions. The serum phosphorus was (1.03 mmol/L, NR: 0.81-1.45), serum magnesium (0.88 mmol/L, NR: 0.65-1.05), 25OHD (83 nmol/L, NR: 75-250), ALP (56 IU/L, NR: 30-129) and 24 hr urine for calcium collection was inadequate.Genetic testing confirmed a heterozygous variant of uncertain significance (VUS) in GNA11 gene c.1-12C>T pArg338Cys which has not been previously reported. The clinical picture is consistent with ADH2. The patient was started on calcium carbonate 500 mg three times daily with meals with follow up in 4 weeks. Conclusion: We report a male patient with hypoparathyroidism who was found to have a novel VUS in GNA 11 gene. This variant could be pathogenic, as the patient presents with a phenotype consistent with ADH2. To date, six different gain-of-function variants in the GNA11 have been identified. An important contribution to the Literature is identifying several variants in ADH2. Presentation: Saturday, July 12, 2025

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