A rare genetic disease can leave people with painful bones, repeated fractures and teeth that fall out too early, yet the condition may remain unrecognized for years.
New research from Central and Eastern Europe suggests that one simple clue in routine blood tests could help doctors identify more people with the disorder.
The condition is called hypophosphatasia, usually shortened to HPP. A study of patients in five European countries was published in 2026 in Frontiers in Endocrinology and found a heavy burden of pain and other health problems.
Healthy bones are not simply solid pieces of calcium. The body constantly builds, repairs and reshapes them, and this process depends on enzymes and minerals working together correctly.
In HPP, a genetic change interferes with one of those important processes. The disease involves the ALPL gene, which provides instructions for making an enzyme needed to help bones and teeth become properly mineralized and strong.
When the enzyme’s activity is too low, bones can remain softer and weaker than normal. Teeth can also be affected because they depend on proper mineralization and strong attachment to the jaw.
HPP is unusual because its severity varies enormously. A severe form beginning before or shortly after birth can be life-threatening, while a milder form may not become obvious until adulthood.
This variation can make diagnosis difficult. An adult with unexplained bone or joint pain, for example, may not immediately appear to have the same genetic condition as a child with bone deformities and early tooth loss.
Researchers wanted to understand how HPP appears among patients in Central and Eastern Europe, where detailed regional information has been limited. They reviewed medical records from Slovakia, Austria, Slovenia, Latvia and Hungary.
The study was retrospective, meaning the researchers looked back at information already recorded during medical care rather than recruiting people and following them forward in time. They began with 49 possible patients and eventually included 34 people who met the study requirements.
Fourteen of the participants were male and 20 were female. All had clinical evidence of HPP together with genetic findings supporting the diagnosis.
The researchers collected information about pain, broken bones, bone deformities and dental problems. They also examined laboratory results, medical imaging, bone density tests and the medicines patients were using.
More than seven in ten patients had chronic pain involving their bones and muscles. For many, controlling that pain required more than one type of pain medicine, suggesting that HPP was having a major effect on everyday life.
Broken bones were also frequent, affecting 44% of the group. About 26% had experienced premature tooth loss, while 18% had bone deformities.
Age at the beginning of the disease appeared to influence the pattern of symptoms. Patients whose HPP started in childhood were more likely to have fractures, bone deformities and early loss of teeth.
Those who developed symptoms during adulthood more often experienced persistent pain and joint problems. This could make adult HPP easier to confuse with other common bone, muscle or rheumatic conditions.
Problems were not limited to the skeleton. Nearly three in ten patients had respiratory complications such as repeated pneumonia, and more than one in ten had kidney stones or calcium deposits in the kidneys.
One result stood out because it could have direct importance for diagnosis. About 97% of the patients had low blood levels of alkaline phosphatase, commonly called ALP.
ALP is routinely measured in many standard blood tests. Doctors often pay close attention when the number is high because high ALP can be associated with liver or bone problems, but a persistently low result may receive less attention.
In HPP, however, low ALP is a major warning sign because the disease directly affects the enzyme. When low ALP occurs repeatedly alongside bone pain, fractures or unusual dental problems, it can provide a reason to investigate HPP.
The study also uncovered a major difference between the number of people suffering from symptoms and the number receiving disease-specific treatment. Only one of the 34 patients was being treated with asfotase alfa, the only approved enzyme replacement therapy that directly addresses the underlying enzyme problem.
There may be several explanations for this low treatment rate. Eligibility rules, cost, availability, age and the severity or timing of symptoms can all affect whether a patient receives a specialized rare-disease therapy.
The finding therefore should not be read as evidence that the other 33 patients were necessarily denied a treatment they should have received. Instead, it raises questions about access to specialists, recognition of HPP and how targeted treatment is being used across different healthcare systems.
The research has limitations because the patient group was small and medical records may not contain every symptom in the same level of detail. The study also cannot tell researchers how common HPP is among the entire population simply by examining a small group of confirmed patients.
Still, rare diseases are difficult to study in large numbers, so information collected across five countries is valuable. The study paints a clear picture of a condition that can affect bones, teeth, muscles, lungs and kidneys while causing substantial long-term pain.
The most useful lesson may be surprisingly simple. A low ALP result, especially when it appears repeatedly in someone with unexplained bone or dental problems, should not automatically be dismissed, because paying attention to that small laboratory clue could help some people reach the correct diagnosis much sooner.
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Source: Frontiers in Endocrinology study authors and participating Central and Eastern European research centers.
