Bone and Mineral Metabolism

SUN-754 - Variable Biochemical Response to Burosumab and Impact of Delayed Diagnosis in X-linked Hypophosphatemia: An Intra-familial Case Series from Mexico

Sunday, June 14, 2026

9:00 AM - 4:00 PM CT

Late-Breaking Poster Presenter(s)

Sayonara Amor Cruz Reyes, MD (she/her/hers)

Internist and Endocrinology Resident
Hospital General de México. National Autonomous University of Mexico (UNAM)
Mexico City, Mexico City, Mexico

Senior Author/Primary Investigator(s)

MF

María Fernanda Flores García, MD

Endocrinology Fellow
Hospital General de México "Dr. Eduardo Liceaga", National Autonomous University of Mexico (UNAM)
Mexico City, Distrito Federal, Mexico

Rapid and Poster Presenter(s)

Sayonara Amor Cruz Reyes, MD (she/her/hers)

Internist and Endocrinology Resident
Hospital General de México. National Autonomous University of Mexico (UNAM)
Mexico City, Mexico City, Mexico

Co-Author(s)

MO

Mariana Olaya Cordova, MD

Endocrinology Fellow
Hospital General de México "Dr. Eduardo Liceaga", National Autonomous University of Mexico (UNAM)
Mexico City, Distrito Federal, Mexico
Guadalupe Manuel Antonio, Second year resident (she/her/hers)

MD
HOSPITAL GENERAL DE MEXICO
Mexico City, Mexico
VS

Valentín Sanchez Pedraza, MD, MSc

Academic Advisor
Hospital General de México "Dr. Eduardo Liceaga", National Autonomous University of Mexico (UNAM)
Mexico City, Distrito Federal, Mexico
JP

Juan Antonio Peralta Calcáneo, MD

Chief of Endocrinology Department
Hospital General de México "Dr. Eduardo Liceaga", National Autonomous University of Mexico (UNAM)
Mexico City, Distrito Federal, Mexico

Background: X-linked hypophosphatemia (XLH) is a rare phosphate-wasting disorder caused by PHEX gene variants, leading to FGF23 excess. While Burosumab has transformed XLH management, data on intra-familial phenotypic variability and response in resource-limited settings remain scarce.

CLINICAL

Case: We report a family of three with genetically confirmed XLH (pathogenic PHEX splice-site variant c.1173+1G>A). The index case, a 31-year-old female, was diagnosed in adulthood after years of skeletal burden, including genu varum and orthopedic surgeries. Initial labs showed phosphorus 2.0 mg/dL [nl 2.5-4.5], hypercalciuria 764 mg/24h [nl 100-300], calcium 8.68 mg/dL [nl 8.80-10.60], and 25(OH)D deficiency. Her two children (male, diagnosed at age 2; female, diagnosed at age 4) presented with growth impairment and limb deformities. After limited success with conventional therapy, all three started Burosumab (male at age 7; female at age 6; mother at age 31) with weight-based dosing.

Results: Burosumab led to clinical improvement in all, but biochemical response varied despite the shared genotype. The adult mother showed a modest increase in phosphorus (2.0 to 2.6 mg/dL [nl 2.5-4.5]). The pediatric female achieved a robust response (2.3 to 3.5 mg/dL [nl 4.0-7.0]). Conversely, the pediatric male exhibited persistent hypophosphatemia (2.7 to 2.6 mg/dL [nl 4.0-7.0]) despite treatment adherence. Notably, the children showed less severe skeletal progression than the mother, highlighting the critical window for early intervention. In Mexico, access to Burosumab remains a significant barrier, often delaying optimal therapy.

Conclusion: This case series demonstrates significant intra-familial variability in Burosumab response, suggesting that factors beyond the PHEX genotype influence outcomes. It underscores the urgency of early diagnosis and the need for improved access to targeted therapies in developing healthcare systems to prevent irreversible skeletal damage.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*