A Hidden Cause of Bone Fragility: Late Diagnosis of Hypophosphatasia in a 40-Year-Old Female

Hypophosphatasia (HPP) is a rare inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene, leading to deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). This results in impaired bone and dental mineralization, causing a wide range of clinical manifestations, from perinatal lethality to mild adult-onset forms. We report a case of a 40-year-old female with a history of joint pain, multiple fractures, dental issues, and bipolar disorder, who was diagnosed with adult-onset HPP. Laboratory investigations revealed persistently low alkaline phosphatase (ALP) levels and elevated vitamin B6. Genetic testing confirmed a pathogenic ALPL mutation. The patient was initiated on enzyme replacement therapy (ERT) with asfotase alfa, resulting in significant symptom improvement. This case highlights the importance of recognizing HPP in adults with unexplained musculoskeletal symptoms and underscores the role of genetic testing in the diagnosis and management of this condition.