An analysis of genetic and health data from over 700,000 individuals confirms previous estimates of Autosomal Dominant Hypocalcemia type 1 (ADH1) prevalence and reveals significant underdiagnosis. Researchers identified nine novel gain-of-function CASR variants associated with ADH1 symptoms and established a connection between CASR and calcium homeostasis regulation in both ADH1 and more complex calcium metabolism disorders like chronic hypoparathyroidism. Approximately 25,000 individuals in the US and EU carry ADH1-causing variants, yet only about 20% have a formal diagnosis.
This research is crucial because it highlights the urgent need for improved diagnostic practices for ADH1. The substantial number of undiagnosed individuals suggests many patients are experiencing debilitating symptoms like seizures, irregular heart rhythms, and muscle cramps without proper treatment. Early diagnosis is essential for effective symptom management and preventing long-term complications like kidney impairment. This information empowers clinicians to consider genetic testing for patients exhibiting related symptoms, facilitating earlier intervention and improving patient outcomes.
The study identified an average frequency of gain-of-function CASR variants of ~3.7 per 100,000, consistent with previous estimates. Furthermore, the discovery of nine novel gain-of-function variants strengthens the link between CASR and ADH1. BridgeBio Pharma’s Phase 3 clinical trial of encaleret for ADH1 is fully enrolled, with topline results expected in the latter half of 2025. A registrational study of encaleret in chronic hypoparathyroidism is planned for 2026.
This research could significantly impact the landscape of hypoparathyroidism diagnosis and treatment. If encaleret proves successful in clinical trials, it could become the first approved therapy for ADH1, offering a much-needed treatment option for this underdiagnosed and often debilitating condition. The planned study in chronic hypoparathyroidism further expands the potential therapeutic applications of encaleret, addressing a broader spectrum of calcium metabolism disorders.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
