FAQ: How Is Hypophosphatasia Diagnosed and What Are the Key Laboratory Markers?

January 2026

In this focused educational video, Heather Mambretti, PA-C, a rheumatology APP with over 12 years of experience and a faculty and board member for RhAPP, explains how hypophosphatasia (HPP) is diagnosed and highlights the key laboratory markers clinicians should not overlook. The discussion reviews the hallmark finding of persistently low serum alkaline phosphatase (ALP), additional supportive labs, characteristic clinical features in adult patients, and the role of imaging and genetic testing in confirming an HPP diagnosis. Designed for APPs and clinicians, this overview emphasizes practical strategies for identifying adult-onset hypophosphatasia, differentiating it from other musculoskeletal conditions, and improving diagnostic confidence in real-world rheumatology practice.