Abstract: SA-PO0523
Beyond Phosphate: Role of Iron in Managing Autosomal Dominant Hypophosphatemic Rickets
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Clinical - 3
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Yang, Feng-Jung, National Taiwan University Hospital, Taipei City, Taiwan
- Tsai, Meng-Ju Melody, National Taiwan University Hospital, Taipei City, Taiwan
- Tung, Yiching, National Taiwan University Hospital, Taipei City, Taiwan
- Lee, Ni-Chung, National Taiwan University Hospital, Taipei City, Taiwan
- Chien, Yin-Hsiu, National Taiwan University Hospital, Taipei City, Taiwan
Introduction
Autosomal Dominant Hypophosphatemic Rickets (ADHR) is a rare phosphate-wasting disorder caused by activating mutations in the FGF23 gene. These mutations impair the cleavage of FGF23, leading to persistent elevations in biologically active intact FGF23 (iFGF23), resulting in renal phosphate wasting and hypophosphatemia. Unlike X-linked hypophosphatemic rickets, ADHR exhibits variable onset, incomplete penetrance, and a remitting-relapsing course, often modulated by systemic iron status. Iron deficiency has emerged as a key regulator of FGF23 transcription and cleavage, with deficiency exacerbating the hypophosphatemic phenotype in ADHR. This case highlights the importance of iron homeostasis in managing phosphate imbalance in ADHR.
Case Description
A 33-year-old woman presented with early-onset bilateral hip fractures and a longstanding history of leg weakness and bone pain. Initial labs revealed severe hypophosphatemia (1.2 mg/dL), elevated iFGF23 (81.25 pg/mL), vitamin D insufficiency, and iron deficiency anemia. Whole exome sequencing confirmed a pathogenic heterozygous variant in FGF23 (c.536G>A, p.Arg179Gln), consistent with ADHR. Her asymptomatic mother carried the same mutation. The patient was treated with phosphate solution, alfacalcidol, and iron supplementation. Following correction of her anemia with IV iron, phosphate and FGF23 levels normalized. Her musculoskeletal symptoms improved, and phosphate and vitamin D analog supplementation were discontinued without recurrence of hypophosphatemia.
Discussion
This case underscores the role of iron deficiency as a modifiable trigger for hypophosphatemia in ADHR. Iron depletion induces increased FGF23 transcription; however, in individuals with FGF23 mutations impairing cleavage, this leads to accumulation of intact FGF23 and subsequent phosphate wasting. Replenishing iron stores not only corrected the anemia but also normalized FGF23 and phosphate levels, eliminating the need for prolonged phosphate therapy. Given the risks of nephrocalcinosis and poor compliance with long-term phosphate supplementation, iron status should be evaluated and optimized in ADHR patients. This case provides further support for individualized, pathophysiology-guided management strategies in hereditary rickets syndromes.