MON-252 An Unusual Presentation of Pseudohypoparathyroidism Type 1a Associated with a Novel GNAS Mutation and Vitamin D Deficiency

Title: An Unusual Presentation of Pseudohypoparathyroidism Type 1a Associated with a Novel GNAS Mutation and Vitamin D Deficiency Background: Pseudohypoparathyroidism type 1a is caused by inactivating mutations in GNAS and is characterized by PTH resistance, resistance to other hormones acting on Gs-coupled receptors, and features of Albright hereditary osteodystrophy (AHO). Type 1b presents with PTH resistance but lacks clinical features of AHO and is caused by methylation defects within GNAS. Pseudohypoparathyroidism is best diagnosed in the setting of normal 25-OH vitamin D levels, as several cases have been reported in the literature that the first stage of vitamin D deficient rickets may mimic pseudohypoparathyroidism, with hypocalcemia, hyperphosphatemia, elevated PTH, and no signs of rickets. Clinical Case: Our patient was a three-year-old female who presented with tonic-clonic seizure activity and tetany and was found to have a calcium of 4.7 mg/dL (8.8-10.8), ionized calcium of 0.5 mmol/L (1-1.5), phosphorus of 10.2 mg/dL (3.2-5.8), PTH of 2597 pg/mL (12-88), alkaline phosphatase of 643 IU/L (100-320), 25-OH Vitamin D of 8.69 ng/mL (20-120), and 1,25-OH Vitamin D of 78.5 pg/mL (19.9-78.5) consistent with both PTH resistance and vitamin D deficiency. TSH was within range but free T4 was low at 0.76 ng/dL (1.08-1.66). Height and growth velocity were normal with obese BMI at the 97%ile. No cataracts, brachydactyly, or subcutaneous calcifications were present, normal dentition was noted, and she was without depressed nasal bridge or round facies. X-rays of bilateral hands and wrists were without brachydactyly or rickets, however, osteopenia was present. Our patient had cut out intake of dairy and eggs one year prior due to a presumed allergy without supplemental vitamin D or calcium intake. She had notable speech and fine motor delays. Family history was significant only for vitamin D deficiency in the maternal grandmother but no history of AHO. Calcium was normalized with a calcium chloride infusion and treatment with calcium carbonate, calcitriol, and cholecalciferol was initiated. Despite 25-OH vitamin D repletion, PTH remained elevated at 1202 pg/mL (12-88), phosphorus remained elevated, and calcium remained slightly low and thus the diagnosis of pseudohypoparathyroidism was confirmed. Genetic testing revealed a novel pathogenic inactivating GNAS mutation at an exon 8 donor splice site consistent with a diagnosis of pseudohypoparathyroidism type 1a. Clinical Lessons: Pseudohypoparathyroidism 1a is most commonly associated with classic signs of AHO such as brachydactyly and subcutaneous calcifications. However, in our patient this disorder presented with only more subtle associated signs. Vitamin D deficiency also clouded the clinical picture, however, laboratory testing in the setting of vitamin D repletion confirmed the diagnosis of pseudohypoparathyroidism.