#418 Hypophosphatasia Genetics: One Gene, Many Presentations

About this episode

How can variants in the same gene cause life-threatening disease in infancy for some individuals, while others experience mild symptoms or remain asymptomatic? Hypophosphatasia (HPP) challenges traditional expectations about genetic inheritance, with both autosomal dominant and autosomal recessive forms and a remarkably broad spectrum of clinical presentations. In this episode, recorded in person in Nashville, our guest is Dr. Kathryn Dahir, Professor of Medicine in the Division of Diabetes, Endocrinology, and Metabolism at Vanderbilt University Medical Center and Director of the Program for Metabolic Bone Disorders. Drawing on decades of experience caring for patients with rare skeletal conditions, Dr. Dahir explores the complex genetics of HPP and why understanding a patient's clinical presentation is just as important as interpreting their genetic test results. The conversation begins with a patient case that challenged Dr. Dahir's understanding of HPP. Initially treated for osteoporosis, the patient experienced recurrent fractures and worsening symptoms despite treatment. Further investigation revealed impaired bone mineralization, low alkaline phosphatase (ALP), and a sing