ESPE Abstracts

Background: Tumor induced osteomalacia (TIO) is clinically characterized by bowed, short and painful legs in children and bone pain if onset in adolescent or adult life. Paraclinical, TIO is characterized by hypophosphatemia, low levels of 1.25-OH₂-vitamin D (1.25 OH₂D), and elevated levels of fibroblast growth factor 23 (FGF23). TIO is due to tumor secretion of FGF23, which inhibits phosphate re-absorption in the proximal renal tubules and the hydroxylation of 25 OH vitamin D to 1.25 OH₂D. The FGF23 tumors are of bone or mesenchymal origin.

Objective: To present the diverse phenotype and treatment options of TIO, we describe the diagnostics and treatment in two children with TIO.

Method: Patient one, a girl, was referred for severe rickets aged 2½ years old. She had a large diffuse hemangioma on the left side of the neck involving all tissue layers and with protrusion into the left oropharynx. Patient two, a girl, had been followed for mental retardation and epilepsy of unknown origin, and was referred for leg pain and hypophosphatemia aged fourteen years old. Both patients had healthy, Caucasian, and unrelated parents.

Results: Both patients had low plasma phosphate and 1.25 OH₂D, elevated alkaline phosphatase and urine phosphate excretion, and a 10-fold increase in plasma FGF23. A blood sample taken directly from the haemangioma of patient one revealed a 25-fold increase in FGF23. Direct sequencing of the PHEX and FGF23 genes of both patients did not show gene variants. Magnetic resonance (MR) angiography in patient one showed a 6x5x4 cm³ haemangiomatous tumor with intraosseous venous malformation in the left skull base and communication with the middle cerebral vein. Due to tumor size and location, surgery was not an option. A treatment trial with intravascular bleomycin sclerotherapy did not reduce tumor size. Treatment was alphacalcidol and phosphate supplementation for 15 years. In January 2020 treatment was changed to burosumab (a FGF23 antibody), 1.4 mg per kg every 4 weeks which resulted in normal 1.25OH₂D and near normal plasma phosphate and FGF23. PET/CT and MRI in patient two revealed an osteolytic tumor of 2.3x3.1x3.6 cm³ in the left scapula. Tumor was surgically removed, leg pain disappeared, and all paraclinical data normalised.

Conclusion: TIO is a very rare condition, and the tumor may be difficult to localize. Treatment is easy if removal of the tumor by surgery is possible. If the tumor is in-operable the FGF23 antibody burosumab today may be an effective treatment option