Oncogenic osteomalacia, raised FGF-23, and renal Fanconi syndrome

Abstract

A 78-year-old female presented in 1996 with bone pain, generalized muscular weakness and immobility. She had marked hypophosphataemia and osteomalacic fractures and a clinical diagnosis of oncogernic osteomalacia was made.1 No tumour could be identified at that time. Subsequent management, including partial parathyroidectomy, oral phosphate and 1,25-dihydroxycholecalciferol (1,25-D3), produced good symptomatic improvement. In 2008, elevated levels of fibroblast growth factor (FGF)-23 were found, 18F-Deoxyglucose PET scanning became available and showed a focus of emission in the right chest (Figure 1a). MRI disclosed a paraspinal tumour at the level of T9 vertebral body (Figure 1b). Further investigations showed that she had a renal Fanconi syndrome, comprising low molecular weight proteinuria, (preoperative results in Figure 2), glycosuria of 2.6–25 mmol/mmol creatinine (reference range <0.1) and aminoaciduria characterized by hyperglycinuria and borderline hyperlysinuria. Preoperative low molecular weight proteinuria was shown by very elevated urinary excretion of both retinol-binding protein (RBP) (Figure 2) and Beta-2-microglobulin (data not shown) relative to albumin.2 The ratio of the renal Transport Maximum of Phosphate/Glomerular Filtration rate, TmP/GFR, a measure of the threshold for urine phosphate reabsorption, was markedly reduced …