Dual Phenotype of Bartter Syndrome Type 2 and Pseudohypoparathyroidism 1b Due to Classic Digenic Inheritance of KCNJ1 and GNAS - A Case Report

Bartter syndrome (BS) Type 2 leads to hypokalemia and nephrocalcinosis. Adult-onset BS2 is rare. Pseudohypoparathyroidism (PHP) 1b is characterized by resistance to parathormone (PTH). The co-occurrence of BS Type 2 and PHP 1b in adults is exceptionally rare, posing diagnostic and therapeutic challenges. A 34-year-old male presented with nephrocalcinosis and carpopedal spasms. Initial evaluations revealed hypokalemia and elevated PTH. Differential diagnoses included PHP, contradicted by nephrocalcinosis and hypokalemia; and Autosomal Dominant Hypocalcemic Hypercalciuria (ADHH), contradicted by elevated PTH. Whole-exome sequencing (WES) identified two mutations: KCNJ1 and GNAS , confirmed by Sanger sequencing of parents. Treatment included potassium, calcium, calcitriol, and thiazides. This case demonstrates complex digenic inheritance, where one genetic mutation modifies the other’s effect. The co-occurrence of two disorders highlights the importance of comprehensive genetic analysis. The treatment strategy requires balancing hypocalcemia and hypercalciuria without worsening other electrolytes.