#408 Low ALP, Fractures, and Early Tooth Loss Point to Hypophosphatasia

Hypophosphatasia (HPP) can present very differently from one person to the next, from life-threatening complications in infancy to fractures, chronic pain, muscle weakness, or early tooth loss later in life. With symptoms spanning multiple body systems and varying across the lifespan, how can clinicians recognize when these seemingly disconnected findings may point to HPP?

In the first episode of our three-part series on hypophosphatasia, we are joined by genetic counselor Amy Patterson to explore the clinical spectrum and diagnosis of HPP. Amy explains what happens biologically in HPP, why traditional age-based classifications do not always capture its variability, and how the condition may present from the prenatal period through adulthood.

We also discuss the importance of persistently low alkaline phosphatase (ALP), including why results must be interpreted using age- and sex-appropriate reference ranges. Amy reviews the additional laboratory findings, medical and dental histories, imaging, physical examination, and molecular testing that may contribute to a diagnosis. She also highlights common misdiagnoses and the clinical clues that should prompt healthcare providers to consider HPP.

Episode Discussion Topics

What hypophosphatasia is and how impaired mineralization affects the body

The perinatal, infantile, childhood, adult, and odonto forms of HPP

Prenatal and infantile presentations of severe HPP

Clinical and dental signs in children

Fractures, chronic pain, fatigue, weakness, and dental concerns in adults

How manifestations may change throughout a person’s lifetime

Variability among relatives with the same familial ALPL variants

Common diagnostic delays and misdiagnoses