SUN-708 Adult-Onset Hypophosphatasia Presenting with Heterotopic Ossification and Dental Manifestations: A Case Report

Abstract Disclosure: L.T. Drake: None. S.S. Dahir: None. C.R. Lichtenfeld: None. L.R. Rehm: None. K.M. Dahir: Alexion Pharmaceuticals, Inc., Ultragenyx, Kyowa Kirin. Background: Hypophosphatasia (HPP) is a rare genetic disorder characterized by defective mineralization of bone/teeth due to mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). HPP clinical presentations vary widely, from severe perinatal forms to milder adult-onset variants. Adult HPP typically presents with recurring fractures, dental abnormalities, and bone pain. Heterotopic ossification, while not commonly associated with HPP, can complicate the diagnostic process. HPP’s variable expressivity and age-dependent symptoms often lead to delayed diagnosis, particularly in adult-onset cases where the presentation may be atypical. Here, we describe an unusual presentation of adult-onset HPP in a female patient, characterized by heterotopic ossification and dental complications. Case Description: A 62-year-old female was referred to orthopedic oncology for a left clavicular mass. Imaging revealed a round mass, with MRI characteristics of an indolent fibrous lesion with peripheral calcification. Physical examination revealed a firm, fixed 3 cm mass above the left clavicle and a 1 cm fixed mass above the left patella. History included early deciduous tooth loss at age 5, bowing deformities requiring bracing as a child, and osteopenia. Laboratory evaluation showed persistently low alkaline phosphatase. Genetic testing confirmed a pathogenic ALPL variant (Het c.1435del). Skeletal survey demonstrated widespread enthesis calcifications and femoral cortical thickening. Bone biopsy showed hydroxyapatite deposits and low bone turnover without osteomalacia. She noted progressive joint pain and recent tooth loss. Conclusions: This case highlights the diagnostic challenges of adult HPP, particularly when presenting with atypical features such as heterotopic ossification. The combination of low serum alkaline phosphatase, ALPL mutation, dental abnormalities, and childhood bone deformities establish the HPP diagnosis despite the unusual presentation with calcified masses. This case emphasizes the importance of considering HPP in adults with unexplained calcified masses and bone pain, even in the absence of frequent fractures. The presence of early dental issues and childhood bone deformities provides crucial diagnostic clues that may help to identify adult HPP cases earlier. Given availability of TNSALP enzyme replacement therapy and ongoing clinical trials, recognition of atypical presentations is crucial for appropriate intervention. Presentation: Sunday, July 13, 2025