Inappropriately Normal: The Fibroblast Growth Factor 23 (FGF23) Illusion, Uncovering a Rare Case of Autosomal Dominant Hypophosphatemic Rickets in Adulthood

Introduction: Hypophosphatemia can result from dietary deficiency, gastrointestinal malabsorption, renal phosphate wasting, or genetic syndromes. Adult-onset hereditary forms like autosomal dominant hypophosphatemic rickets (ADHR) are rare and often diagnosed after complications emerge. FGF23 plays a key role in phosphate regulation, and its inappropriately normal levels may still indicate pathology in hypophosphatemia. Case Description: A 38-year-old woman presented with chronic hypophosphatemia, progressive lower extremity bowing, neuropathy, hypertension, and flank pain. She had a remote history of partial colectomy at age 15. Physical exam pertinent for bowing of her lower extremities. Labs showed: serum phosphorus 1.5 mg/dL, ionized calcium 1.13 mmol/L, total calcium 9.0 mg/dL, PTH 56 pg/mL, and vitamin D 40 ng/mL. A 24-hour urine revealed phosphaturia of 1 g/day. Glycosuria and other electrolyte losses were absent. Despite phosphate supplementation, serum phosphorus remained low. FGF23 was 39 pg/mL (ref <59), inappropriately normal for the level of hypophosphatemia. Genetic testing revealed a heterozygous FGF23 mutation (c.734G>A, p.Arg245His), confirming ADHR in her clinical scenario. Discussion: ADHR results from mutations that impair FGF23 degradation, prolonging its phosphaturic effect. Even with FGF23 in the normal range, its activity may be excessive. Conventional treatment with phosphate and calcitriol may be insufficient. Burosumab, an anti-FGF23 monoclonal antibody, offers targeted therapy. This case underscores the diagnostic and therapeutic challenges of hereditary hypophosphatemia in adults. Genetic testing offers valuable insights but must be carefully interpreted in the clinical context. The presence of an FGF23 mutation, even with borderline normal activity, underscores the importance of careful laboratory interpretion which allows tailored treatment hence, prevention of nephrocalcinosis and skeletal deformities even when found in adulthood.