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Two Case Reports of FGF23-Induced Hypophosphatemia in Childhood Biliary Atresia
Halley Wasserman1, Chijioke Ikomi2, Einar T Hafberg3
1Divisions of Endocrinology, Halley.wasserman@cchmc.org.
Insights
Biliary atresia (BA) in infants can cause hypophosphatemic rickets due to elevated fibroblast growth factor 23 (FGF23). Liver transplantation normalized FGF23 levels, resolving rickets and phosphate wasting.
Area of Science:
- Pediatric Gastroenterology and Hepatology
- Endocrinology and Metabolism
- Pediatric Bone Diseases
Background:
- Cholestatic liver disease is linked to rickets from impaired vitamin D absorption.
- Elevated fibroblast growth factor 23 (FGF23) causes hypophosphatemic rickets in children.
- Biliary atresia (BA) is a severe form of neonatal cholestasis requiring liver transplantation.
Observation:
- Two infants with end-stage liver disease due to BA presented with hypophosphatemia and renal phosphate wasting.
- Both infants had markedly elevated serum FGF23 levels (over 8x upper limit of normal).
- The older infant exhibited radiographic signs of rickets, requiring significant phosphate and calcitriol supplementation.
Findings:
- Serum FGF23 levels normalized post-liver transplantation in both infants.
- Phosphate and calcitriol supplementation was successfully discontinued after transplantation.
- Immunohistochemistry showed ectopic FGF23 overexpression in hepatocytes of the BA liver, suggesting a direct link.
Implications:
- This study identifies a novel cause of hypophosphatemic rickets in infants with biliary atresia.
- It highlights FGF23 as a key mediator in BA-associated bone disease.
- Further research is warranted to explore the relationship between cholestatic disorders and bone metabolism.
Abstract:
Cholestatic liver disease has long been associated with childhood rickets, secondary to impaired absorption of fat-soluble vitamin D. Elevated serum levels of fibroblast growth factor 23 (FGF23), secondary to genetic defects or tumor-induced osteomalacia, causes hypophosphatemic rickets in childhood. We present 2 infants with end-stage liver disease due to biliary atresia (BA) who developed hypophosphatemia with renal phosphate wasting. Serum FGF23 levels were elevated more than 8 times the upper limit of normal, and the older infant showed radiographic evidence of rickets. Both infants required large supplements of phosphate in addition to calcitriol. Following liver transplantation, FGF23 normalized in both patients and phosphate and calcitriol supplementation were discontinued. Immunohistochemistry revealed ectopic overexpression of FGF23 by hepatocytes in the BA liver. These observations highlight a unique cause of hypophosphatemic rickets in childhood and suggest the need for further investigation into the relationship between BA and other cholestatic disorders, and bone metabolism.
