Novel Human Genetics Evidence Confirms Estimates of Genetic Prevalence, Underdiagnosis, and Potentially Greater Symptom Burden of Gain-of-Function CASR Variants Associated with ADH1

Core Insights - The study confirms the genetic prevalence of Autosomal Dominant Hypocalcemia Type 1 (ADH1) and highlights a significant gap in diagnosis and care for affected individuals [1][2][3] Group 1: Genetic Findings - The average frequency of gain-of-function CASR variants is approximately 3.7 per 100,000, equating to around 25,000 carriers in the US and EU [1][6] - Only about 20% of individuals with genetic variants linked to ADH1 have an established diagnosis, indicating a major gap in disease recognition [1][2] - Nine novel gain-of-function CASR variants were identified, associated with symptoms consistent with ADH1 [1] Group 2: Clinical Implications - ADH1 is a common genetic form of hypoparathyroidism, presenting serious symptoms like seizures and irregular heart rhythms due to hypocalcemia [2][5] - The findings emphasize the importance of genetic testing in uncovering the underlying causes of hypoparathyroidism [2][3] Group 3: Clinical Trials and Future Developments - BridgeBio's Phase 3 clinical trial of encaleret for ADH1 is fully enrolled with 71 participants, expected to report topline results in the second half of 2025 [4] - If successful, encaleret would be the first approved therapy for ADH1, with plans to initiate a study in chronic hypoparathyroidism in 2026 [4][8] Group 4: Company Overview - BridgeBio Pharma focuses on discovering and delivering transformative medicines for genetic diseases, with a commitment to applying advances in genetic medicine [9]