Burosumab treatment for FGF23-related hypophosphatemia in a two-year-old girl with McCune-Albright syndrome

Sep 30, 2026

McCune-Albright syndrome (MAS) is a rare mosaic disorder driven by a gain-of-function GNAS variant, producing endocrine and skeletal manifestations including fibrous dysplasia (FD) and FGF23-related hypophosphatemia. Conventional approaches such as phosphate supplementation and vitamin D analogs show limited efficacy in MAS. This case report describes a 2-year-old girl with MAS complicated by hyperthyroidism, gonadotropin-independent precocious puberty, excess GH, Cushing syndrome, FD, and FGF23-related hypophosphatemia. Genetic testing confirmed a pathogenic GNAS variant (p.Arg201Cys). By 16 months she had over seven fractures; burosumab therapy normalized serum phosphate, improved renal phosphate handling, resolved bone pain, and prevented further fractures through age 4 years and 6 months.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Highlights

Abstract

Key words

Introduction

Clinical Pediatric Endocrinology Vol.35 / No.1 January 2026 pp 110–106 Case Report Burosumab treatment for FGF23-related hypophosphatemiain a two-year-old girl with McCune-Albright syndrome Tomoki Saito1 , Kana Hiromoto2 , Naoya Morisada2, 3 , Ryosuke Sakata4 , Tomohiro Ishii5 , Tomonobu Hasegawa6 , Keiichi Ozono7 , and Kayo Ozaki1 1Department of Endocrinology and Metabolism, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan 2Department of Genome Medical Center, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan 3Department of Clinical Genetics, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan 4Department of Orthopedic Surgery, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan 5Department of Endocrinology and Metabolism, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan 6Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan 7Center for Promoting Treatment of Intractable Diseases, ISEIKAI International General Hospital, Osaka, Japan Highlights ● MAS causes FGF23-related hypophosphatemia and fractures in some patients. ● Burosumab normalized phosphate and reduced fractures in our patient with MAS. ● Burosumab may improve the prognosis of patients with MAS and hypophosphatemia. Abstract. McCune-Albright syndrome (MAS) is a rare mosaic disorder caused by a gain-of-function pathogenic GNAS variant that triggers endocrine and skeletal manifestations, including fibrous dysplasia (FD) and FGF23-related hypophosphatemia. Conventional treatments (e.g., phosphate supplementation, vitamin D analogs) have shown limited efficacy against MAS. Burosumab, a monoclonal FGF23-targeting antibody, has recently been reported as a potential treatment. We report the case of a 2-yr-old girl with MAS complicated by hyperthyroidism, gonadotropinindependent precocious puberty, excess GH, Cushing syndrome, FD, and FGF23-related hypophosphatemia. Genetic testing confirmed a pathogenic GNAS variant (p.Arg201Cys) . By the age of 16 mo, she experienced > 7 fractures. Burosumab (1 .0 mg/kg bi-weekly) was administered at age 2 yr and 3 mo. Her serum phosphate levels normalized, tubular maximum reabsorption of phosphate-to-glomerular filtration rate ratio improved, bone pain resolved, and she experienced no further fractures since 2 yr and 7 mo, as of age 4 yr and 6 mo. To our knowledge, our patient is the youngest MAS patient treated with burosumab and the second reported case to receive burosumab among patients with genetically confirmed MAS. Burosumab improved biochemical abnormalities related to excess FGF23 and reduced fracture occurrence in our patient, supporting its efficacy in treating FGF23-related hypophosphatemia due to MAS. Key words: burosumab, FGF23, fibrous dysplasia, GNAS, hypophosphatemia, McCune-Albright syndrome Received: July 21, 2025 Accepted: September 25, 2025 Advanced Epub: October 5, 2025 Corresponding author: Tomoki Saito, M.D., Department of Endocrinology and Metabolism, Hyogo Prefectural Kobe Children’s Hospital, 1-6-7 Minatojima Minamicho, Chuo-ku, Kobe, Hyogo 650-0047, Japan E-mail: [t.saito.rq@gmail.com](t.saito.rq@gmail.com) This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial No Derivatives (by-nc-nd) License <[http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)> . Copyright© 2026 by The Japanese Society for Pediatric Endocrinology Clin Pediatr Endocrinol 111 Introduction McCune-Albright syndrome (MAS) is a rare mosaic disorder caused by a gain-of-function pathogenic variant of the GNAS gene. This gene encodes the Gαs protein, which mediates intracellular signaling for various hormone receptors. Gαs activation causes various clinical manifestations, including fibrous dysplasia (FD), café au-lait macules, gonadotropin-independent precocious puberty, non-autoimmune hyperthyroidism, excess growth hormone (GH) levels, and Cu

FAQs

What condition is described and what genetic change was confirmed in the case?

The case describes a 2-year-old girl with McCune-Albright syndrome complicated by FGF23-related hypophosphatemia. Genetic testing confirmed a pathogenic GNAS variant (p.Arg201Cys).

What treatment was used and how was it administered?

Burosumab was administered at age 2 years and 3 months at a dose of 1.0 mg/kg bi-weekly.

What clinical and biochemical outcomes were observed after burosumab therapy?

Serum phosphate levels normalized, tubular maximum reabsorption/phosphate-to-glomerular filtration rate ratio improved, bone pain resolved, and no further fractures occurred after treatment through the reported follow-up period.

Sep 30, 2026

Uploaded by MrHarris58