Abstract Background Fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets/osteomalacia arises from excessive FGF23 activity, with X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO) as the most common congenital and acquired forms, respectively. However, in a substantial subset of patients with acquired FGF23-related hypophosphatemic osteomalacia, phosphaturic mesenchymal tumors (PMTs) remain undetectable despite extensive imaging studies. A recent study identified autoantibodies against PHEX, the gene responsible for XLH, in 5 of 13 patients with acquired FGF23-related osteomalacia without detectable PMTs, thereby defining a novel disease entity termed autoimmune osteomalacia (AIO). Clinically, AIO presents with milder disease activity than TIO, comparable in severity to XLH. Findings Some patients exhibited concomitant autoimmune disorders, and whole-genome sequencing revealed rare variants in autoimmune susceptibility genes, suggesting a genetic predisposition. Therapeutic options include burosumab and, potentially, immunosuppressive therapy such as glucocorticoids. Long-term follow-up indicates that AIO patients may develop ectopic ossifi cation, similar to XLH. Anti-PHEX autoantibodies were detected using both luciferase immunoprecipitation systems and fl ow cytometry, underscoring the importance of complementary methods for detecting antibodies against native conformational epitopes. Conclusions Recognition of AIO should be particularly considered in patients with acquired FGF23-related hypophosphatemia who have undetectable PMTs, relatively mild disease activity, and concurrent autoimmune diseases.
Hoshino et al. (Sat,) studied this question.
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