SAT-297 Pseudohypoparathyroidism Type 1B: A Rare but Manageable Cause of Bone Disease

Abstract K.L. Flint: None. H. Jueppner: None. M. Reyes: None. E.W. Yu: None. Introduction: Pseudohypoparathyroidism (PHP) refers to the set of diseases characterized by end organ resistance to PTH and frequently other hormones, particularly TSH. PHP1A and PHP1B are the most common subtypes of PHP that lead to PTH-resistance at the level of the proximal renal tubules, but not the distal tubules or bones. Clinical Case: A 27 year old female presented to clinic with chronic hypocalcemia and elevated PTH. Seven years prior to the visit, she had traumatic fractures of her face and humerus and was found to have hypocalcemia to 7.7 mg/dl (normal 8.5-10.5 mg/dl). Her hypocalcemia went untreated at that time. In the year prior to the current visit, her serum calcium was 6.9-7.6 mg/dl with normal albumin, and PTH was markedly elevated to 991 pg/ml (normal 10-60 pg/ml). She was not taking calcium supplements, reported low dietary calcium, and denied bony pain or dental problems. She had delayed menarche (age 17). Exam was notable for BMI 41, positive Chvostek’s sign, and no overt brachydactyly or other features of Albright’s hereditary osteodystrophy. Labs were notable for elevated bone-specific alkaline phosphatase 260 IU/L (normal 12.1-42.7 IU/L), normal 25-hydroxy-vitamin D, phosphorus, albumin, renal function, and thyroid hormone. Imaging demonstrated endosteal resorption, possible foreshortening of the left fourth metatarsal, and a lucent lesion in the left foot consistent with a brown tumor due to longstanding secondary hyperparathyroidism. MLPA (multiplex ligation-dependent probe amplification) provided no evidence for a deletion or duplication at GNAS. MS-MLPA (methylation-sensitive MLPA) revealed loss-of-methylation at the maternal GNAS differentially methylated regions (DMRs) (A/B, XL, and AS) and gain-of-methylation at the paternal NESP DMR; these findings are consistent with sporadic PHP1B. Six microsatellite markers in the chr20q13 region showed heterozygosity, making a duplication of the paternal chromosome 20q (patUPD20q) unlikely. We started treatment with calcium supplements and calcitriol, but the patient missed her follow-up lab appointment. Conclusions: PHP1B is a rare condition in which patients have PTH-resistance at the level of the proximal renal tubules but not at the bones, leading to hypocalcemia and secondary hyperparathyroidism. When left untreated, longstanding hyperparathyroidism can lead to endosteal bone resorption and osteolytic lesions termed brown tumors. Although PHP1B is typically diagnosed in puberty, it is important to include PHP in the differential of an adult presenting with hypocalcemia and hyperparathyroidism to prevent life-threatening complications of severe calcium and PTH imbalance. Genetic and epigenetic testing can help differentiate between autosomal dominant forms caused by heritable genetic changes, and sporadic forms that have characteristic epigenetic changes without a clear genetic defect. Saturday, June 1, 2024