Rare Forms of Hereditary Hypoparathyroidism: Delayed Diagnosis Due To Atypical Disease Onset

Background: Hereditary hypoparathyroidism (hypoPT) is a rare endocrine disorder caused by absent or insufficient parathyroid hormone secretion. Genetic forms are uncommon and frequently underdiagnosed, particularly when clinical onset is atypical.Purpose: We present three cases of genetic hypoPT caused by CASR, GNA11, and GATA3 mutations, highlighting diagnostic challenges and management approaches.Methods: Clinical data, biochemical results, and genetic findings were collected for three female patients with early-onset, nonsurgical hypoPT. Each case was evaluated for presenting symptoms, comorbidities, treatment responses, and outcomes. Relevant literature and guidelines were reviewed for context and management recommendations.Results: All patients exhibited chronic hypocalcemia, hyperphosphatemia, and low PTH without prior neck surgery. Initial manifestations were atypical, delaying diagnosis until adolescence or adulthood. Case 1 (CASR mutation) presented with seizure-like episodes misdiagnosed as epilepsy, and partial response to calcium–vitamin D therapy. Case 2 (GNA11 mutation) showed Raynaud’s phenomenon, dermatologic symptoms, and treatment intolerance without nephrocalcinosis. Case 3 (GATA3 mutation) had early deafness, later renal impairment, and fluctuating calcium levels. Genetic testing confirmed pathogenic variants, and individualized management with active vitamin D analogs achieved partial biochemical control. All patients remain under multidisciplinary follow-up with stabilization of neurological complications and monitoring of renal status. Conclusion: Genetic causes of hypoPT should be suspected in patients with early-onset or atypical presentations in the absence of neck surgery. Timely genetic testing confirms the diagnosis and determines personalized therapy. Management requires careful titration of calcium and active vitamin D to avoid complications and may benefit from emerging treatments (long-acting PTH analogs). Early recognition and tailored interventions can improve patient outcomes and quality of life.