Pseudohypoparathyroidism type 1B mimicking gitelman syndrome: diagnostic pitfalls and molecular insights.

Objective: Pseudohypoparathyroidism type 1B (PHP1B), caused by abnormal methylation of the Methods: Retrospective analysis of five patients initially misdiagnosed with GS due to hypokalemia but ultimately confirmed as PHP1B were collected. Whole-exome sequencing (WES) was used to exclude mutations in genes associated with renal tubular diseases, and methylation-sensitive multiplex ligation-dependent probe amplification (MS-MLPA) was employed to assess Results: Patients (median age 48 years; 60% female) had prolonged diagnostic delays (median 11 years). Universal clinical manifestations included muscle cramps and weakness. Biochemical profiling revealed hypokalemia (mean potassium 3.14 mmol/L), hypocalcemia (mean calcium 1.55 mmol/L), and elevated PTH (mean 422.1 pg/mL). All patients exhibited intracranial calcifications, predominantly in the basal ganglia. Genetic testing excluded Bartter/Gitelman syndromes, while MS-MLPA identified multi-differentially methylated region defects (NESP hypermethylation with AS1/XL/A/B hypomethylation) in four patients and isolated A/B hypomethylation with heterozygous Conclusion: PHP1B can present with nonspecific hypokalemia, mimicking GS. Definitive diagnosis requires combined WES and methylation analysis, particularly in WES-negative cases with PTH resistance and intracranial calcifications. Therapeutic focus should prioritize calcium/calcitriol over potassium supplementation, with epigenetic heterogeneity guiding long-term management.