SUN-732 Atypical Presentation of a Rare Bone Disease in Adolescence: A Rare Case Report

Abstract Disclosure: L.R. Rehm: None. L.T. Drake: None. S.S. Dahir: None. C.R. Lichrenfeld: None. K.M. Dahir: Alexion Pharmaceuticals, Inc., Kyowa Kirin, Ultragenyx. Background: Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder that causes ostealgia due to bone inflammation without any underlying infection. Typically, this is a diagnosis of exclusion. CRMO often appears in children at age 9 or 10 and can lead to bone deformities or irregular bone growth patterns. Hypophosphatasia (HPP) is an inherited disorder caused by variants in the gene ALPL that affects bone and tooth development. HPP disrupts the body's mineralization process, resulting in abnormal mineral deposits throughout the skeletal structure and impacting bone growth. Case Description: A 22-year-old female suffered pain in her femur, hips, pelvis, humerus, hand, foot, and wrist. At the age of 12 she developed debilitating jaw pain requiring a biopsy and extraction of two teeth. Malignancy and an infectious etiology were excluded, she was diagnosed with CRMO and referred to rheumatology. NSAIDs proved ineffective, leading to treatment with prednisone and linezolid from ages 12 to 18, with periods requiring high doses of steroids for pain relief. Furthermore, the patient suffered from both acute pain and generalized bone/muscle pain. At 16, the patient had bilateral metatarsal stress fractures, arthralgias, fatigue, back pain, migraines, and POTS. She transferred to an adult clinic at age 18, laboratory tests revealed low AlkP of 19 U/L (rr 40-150 U/L) and elevated B6 of 287.2 nmol/L (rr 20-125 nmol/L). A review of the EHR showed a persistently low AlkP since the age of 19 days, which was below the age-adjusted reference range at 65U/L (rr 150-400 U/L) but had not been clinically recognized. As a young adult, the patient reported progressive, widespread bone and muscle pain that significantly limited her daily activities. Genetic testing identified a heterozygous pathogenic variant in ALPL (c.1171C>T). Since her initial visit in the adult endocrinology clinic, she has had additional bilateral metatarsal stress fractures. Discussions are underway to initiate ERT. Conclusions: A deficiency in tissue nonspecific alkaline phosphatase (TNAP) causes HPP. TNAP plays a critical role in mineralization by dephosphorylating inorganic pyrophosphate (PPi), a mineralization inhibitor produced from adenosine triphosphate (ATP) through the action of ectonucleotide pyrophosphatase phosphodiesterase 1 (NPP1). CRMO has been reported in association with HPP. Given the variable phenotypes and atypical presentations of HPP, increased awareness of these variations is essential. Accurate diagnosis of HPP and CRMO is important to avoid unnecessary glucocorticoid exposure. Further research is needed to better understand the relationship between HPP and CRMO. Presentation: Sunday, July 13, 2025