title: Polyostotic osteolysis and hypophosphatemic rickets with elevated serum fibroblast growth factor 23: A case report.
abstract: We report on a boy who presented with hypophosphatemic rickets with elevated serum fibroblast growth factor 23 (FGF23) and polyostotic osteolytic lesions at age 2 years. Tumor-induced hypophosphatemic rickets was suspected; however, bone biopsy for osteolytic changes revealed no tumorous change, except for irregularly dilated vessels associated with osteoclasts and fibrous proliferation. Venous sampling failed to point to FGF23-producing foci. After alfacalcidol and phosphate supplementation, the rachitic skeletal changes improved, but FGF23 increased and new osteolytic lesions developed. Serum levels of neopterin and a few cytokines, including plasma transforming growth factor-β and soluble tumor necrosis factor receptor type II, were elevated. At age 4 years, high doses of phosphate resulted in increased serum phosphate levels, decreased neopterin and cytokines, decreased FGF23, and stabilization of osteolysis. We excluded germline mutations in PHEX, FGF23, DMP1, and ENPP1 (genes for hereditary hypophosphatemic rickets) and somatic mutations in the GNAS and HRAS/KRAS (the disease-causing genes for McCune-Albright syndrome and linear nevus sebaceous syndrome, respectively). We could not perform octreotide scintigraphy or fluorodeoxyglucose-positron emission tomography, and thus could not completely exclude occult FGF23-producing tumors. However, considering the course of the disease, it is intriguing to assume that dysregulation of osteoclast-macrophage lineage may have induced increased neopterin levels, increased cytokine levels, osteolytic process, and possibly FGF23 overproduction.
authors.affiliation: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.|Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Muroya
authors.affiliation: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Asakura
authors.affiliation: Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
authors.affiliation: Department of Radiology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.affiliation: Department of Radiology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Aida
authors.affiliation: Department of Orthopedic Surgery, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Machida
authors.affiliation: Department of Pathology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Adachi
mesh_terms: D049109:Cell Proliferation; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood / Q000235:genetics; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005359:Fibrous Dysplasia, Polyostotic / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use; D008297:Male; D019798:Neopterin / Q000097:blood / Q000235:genetics; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010014:Osteolysis / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010710:Phosphates / Q000627:therapeutic use; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood / Q000235:genetics; D063730:Rickets, Hypophosphatemic / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000097:blood / Q000235:genetics
chemical_list: D016207:Cytokines; C000717427:FGF23 protein, human; D006887:Hydroxycholecalciferols; D010710:Phosphates; D047889:Receptors, Tumor Necrosis Factor, Type II; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors; D019798:Neopterin; D000089703:Fibroblast Growth Factor-23; C008088:alfacalcidol
keywords: fibroblast growth factor 23; hypophosphatemic rickets; polyostotic osteolysis