SUN-713 Challenges in the management of pregnancy in a woman with XLH undergoing burosumab treatment

Abstract Disclosure: A.G. Diaz: None. R.A. Salazar Muñoz: None. R. Saldivar: None. M. Rodrigo: None. M.A. Poch: None. S.P. Lucas: None. X-linked hypophosphatemia (XLH) is a genetic disorder caused by mutations in the PHEX gene, leading to FGF23 excess. This results in renal phosphate wasting and reduced levels of 1,25(OH)₂D, causing hypophosphatemia and rickets/osteomalacia. Burosumab, an anti-FGF23 monoclonal antibody, restores serum phosphate levels and mitigates the effects of XLH. During pregnancy, fetal serum phosphorus levels are maintained higher than maternal levels to support bone development. The placenta is crucial in the active transcellular transport of minerals from the maternal circulation. Studies in XLH animal models have shown that fetal serum phosphorus levels remain stable despite maternal hypophosphatemia. FGF23 does not cross the placenta, and high fetal FGF23 levels do not affect phosphate excretion, serum phosphorus, amniotic fluid phosphate levels, placental phosphate transport, skeletal development, or bone mineralization, suggesting that fetal FGF23 does not play a significant role in phosphorus homeostasis in utero. Currently, no data exist on the use of burosumab during human pregnancy. Animal studies have demonstrated toxicity, and its use is not recommended during pregnancy or in fertile women who are not using contraception. Case Study: A 23-y.o woman with XLH diagnosed at age 2 and initially treated with phosphate and calcitriol. Genetic testing confirmed a heterozygous PHEX mutation. In December 2020, due to chronic joint and muscle pain, she began burosumab therapy. Three years later, she became pregnant, discontinued burosumab and resumed phosphate and calcitriol. At 11 weeks, she had a miscarriage and restarted burosumab. Despite contraceptive and genetics counseling, she conceived again four months later, discontinued burosumab and resumed conventional therapy. The pregnancy progressed without complications. Phosphate supplementation was adjusted but remained limited due to gastrointestinal intolerance, reaching a 70% higher dose. Calcitriol was raised by 50% in late pregnancy. However, fasting serum phosphate remained low, while serum calcium and urinary calcium excretion showed no changes. Serum alkaline phosphatase rose slightly in the third trimester, and 25(OH)D remained low despite adding 5,000 IU/day of D₃. She delivered via cesarean section at 35 weeks. The neonate, a male, weighed 2,015 g and measured 50 cm in length. He exhibited hypophosphatemia on day 2 of life, and genetic analysis confirmed the PHEX mutation. Echocardiography revealed pulmonary stenosis with a patent ductus arteriosus, requiring surgical intervention. Lactation continued for six months, after which burosumab treatment was resumed due to severe pain. Conclusion: This is the first report of pregnancy in a XLH woman undergoing burosumab therapy. Burosumab appears to be safe during conception. Real-world data are necessary to evaluate its long-term safety and confirm this finding. Presentation: Sunday, July 13, 2025