A rare genetic bone disorder causes significant symptoms affecting many aspects of life, yet most patients remain untreated, according to a study published in Frontiers in Endocrinology.
Researchers reviewed medical records of 34 patients with clinically and genetically confirmed hypophosphatasia (HPP) across five Central and Eastern European countries: Slovakia, Austria, Slovenia, Latvia, and Hungary. HPP is caused by mutations in the ALPL gene, which produces an enzyme essential for the mineralisation of bones and teeth.
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More than 70% of patients experienced chronic musculoskeletal pain, with most requiring multiple pain medications to manage daily life. Overall, 44% of patients had fractures, 26% experienced premature tooth loss, and 18% developed bone deformities. The disease’s impact extended beyond the skeleton, with nearly 30% experiencing respiratory complications including recurrent pneumonia, and over 10% developing kidney stones or calcium deposits.
Symptoms varied by age of onset. Patients whose disease began in childhood were more likely to develop bone deformities, frequent fractures, and early tooth loss. Those with adult-onset symptoms more commonly experienced persistent pain and joint problems.
Nearly all patients (97%) had low blood levels of alkaline phosphatase, the hallmark diagnostic sign of HPP. However, only one of the 34 patients was receiving asfotase alfa, an enzyme replacement therapy that is currently the only approved treatment for the disorder.
The researchers noted that this diagnostic marker is often missed in routine clinical practice. HPP can range from mild to life-threatening, potentially causing breathing difficulties and seizures in infants in severe cases. More than 450 disease-causing variants of the ALPL gene have been identified.
The findings highlight significant gaps in awareness and access to rare disease therapies across the region.
Source: Medical Xpress / Frontiers in Endocrinology (2026)
