What is hypophosphatasia (HPP)?
Many signs of HPP — fatigue, muscle pain, and a history of injuries — can be mistaken as a "normal" part of life. However, for those living with HPP these symptoms are usually more complicated, become more challenging over time, and can be harder to manage.
HPP can also look a lot like other conditions such as osteoporosis, arthritis, or fibromyalgia.
HPP can also look a lot like other conditions such as osteoporosis, arthritis, or fibromyalgia.
While the true number of people with HPP remains unknown, estimates suggest it is around 1 in 5,700 people, with many remaining undiagnosed.1,2*
1. Tornero C, et al. Orphanet J Rare Dis. 2020;15(1):51.
2. Data on File, Alexion 2025.
*Prevalence data estimated based on Tornero C, et al. 2020, a cross-sectional study of 1,536,711 laboratory ALP
records from 386,353 subjects conducted at La Paz Hospital, Madrid, Spain, 2009–2015.
HPP is an inherited condition. This means it runs in families and multiple relatives could be affected.
It can affect both children and adults, with symptoms sometimes appearing before birth or developing at any age.
It can affect both children and adults, with symptoms sometimes appearing before birth or developing at any age.
HPP may evolve over a person's lifetime. Follow the links for more information about symptoms in children and adults.
HPP can appear in utero. In such cases, it’s associated with life-threatening symptoms. Signs typically include abnormalities in the way bones have formed.
Symptoms of HPP in infants aged <6 months include noticeable differences in bone formation, breathing problems, issues with feeding, weight gain, seizures, kidney problems and other developmental challenges.
After 6 months and up to 18 years old, HPP symptoms can vary. They commonly include slow growth, falling behind in key developmental milestones, such as walking or riding a bike, early loss of deciduous or permanent teeth, and pain.
After age 18, HPP symptoms can differ a lot from person to person and are often mistaken for other conditions. Adults may experience fatigue, pain, weak muscles, joint problems like pseudogout, and frequent or slow-healing fractures.
HPP is caused by persistently low activity of an enzyme called alkaline phosphatase (ALP).
In order for our bodies to carry out their usual functions, we rely on the help of special proteins, called enzymes, that are in charge of building some substances and breaking others down. An enzyme named ALP and two essential components, calcium and phosphate, play a key role in forming and maintaining healthy bones.
People with HPP have persistently low ALP. This is caused by an inherited change (variant) in the ALPL gene. Low activity levels of the ALP enzyme is a key lab finding that helps distinguish HPP from other conditions.
HPP can be inherited in two ways. If both parents pass on a changed ALPL gene (recessive), symptoms can sometimes be life-threatening. If only one parent passes it on (dominant), HPP can still occur, but symptoms can vary widely.
However, inheritance patterns do not always predict how HPP will affect an individual. People with the same genetic change can experience very different symptoms, even within the same family. This variation is likely influenced by a combination of genetics, environment, and other factors that researchers are still working to understand, including the possible role of other “modifier” genes.
However, inheritance patterns do not always predict how HPP will affect an individual. People with the same genetic change can experience very different symptoms, even within the same family. This variation is likely influenced by a combination of genetics, environment, and other factors that researchers are still working to understand, including the possible role of other “modifier” genes.
The information provided in this material is intended as a source of education for the general public. It is not intended for any self-diagnosis purposes nor to replace the advice of your doctor or healthcare professional. Please consult your doctor or healthcare professional if you have any questions or concerns.