G580(P) Tumour induced osteomalacia: delayed diagnosis of a rare disorder with a common presentation

Abstract

Case history A 4 year old, previously well male child developed progressive weakness of lower limbs manifesting as frequent falls and difficulty in lifting himself up. Over the next nine months he lost his ability to climb stairs and run and became wheelchair bound. During this course he also developed bony deformity of knees. On examination there was profound proximal muscle weakness in the lower limbs. Bilateral genu valgum became more obvious during the later stages. He underwent extensive investigation for neuromuscular disease, but a definitive diagnosis could not be made initially. Investigations His 25 hydroxy Vitamin D level was insufficient (38 nmol/L) with a low serum phosphate level. Investigations for neuromuscular disorders were negative, with a normal CPK, SMN gene and MRI brain. A bone profile repeated almost a year after initial presentation, showed persistently low plasma phosphate (0.6 mmol/L) with normal calcium, mildly elevated alkaline phosphatase and normal PTH (parathyroid hormone) levels. Tubular reabsorption of phosphate was inappropriately low (86%). A knee X-ray confirmed rickets. Genetics for PHEX, ENPP1, DMP1 and SLC34A3 were negative. FGF 23 (fibroblast growth factor) levels 234 HRU/mL (normal Diagnosis A diagnosis of tumour induced osteomalacia was made based on marked muscle weakness with classical knee deformity, biochemistry, radiological features and negative genetics. Discussion Low phosphate level in this case, was initially attributed to Vitamin D deficiency. In addition as alkaline phosphatase and PTH levels were normal, rickets was missed, delaying diagnosis. X- linked hypophosphataemic rickets is the commonest cause of hypophosphataemic rickets. Negative genetics for hypophosphatemic rickets in this child raises the possibility of TIO. TIO is a paraneoplastic syndrome caused by tumours that secrete FGF 23. It is rare in children. Tumors may be difficult to locate, with a negative octreotide scan in 40% cases. Our patient has improved with alfacalcidol and phosphate supplements, but may benefit from the FGF23 antibody Burosumab. Learning points Muscle weakness is an unusual feature of hypophosphataemic rickets and should alert the clinician to this rare disorder.