Tumoral Calcinosis

Abstract

Abstract: Tumoral calcinosis (TC) is a disorder of enhanced renal tubular phosphate reabsorption resulting in hyperphosphatemia and ectopic calcifications. Gene analyses have confirmed that destabilizing mutations within fibroblast growth factor-23 (FGF23) and GalNAc transferase-3 (GALNT3) are responsible for heritable TC. Herein, we present a patient with phenotypic and biochemical features of TC, whose evaluation revealed no mutations in either the FGF23 or GALNT3 genes and normal circulating C-terminal and intact FGF23 concentrations. The patient is a 12-year-old African American man with ectopic, subcutaneous mineral deposits, with a diagnosis of tumoral calcinosis based on collective clinical features. Plasma FGF23 concentrations were determined using both an assay that measures full-length FGF23 and one that recognizes the C-terminal portion. Gene analysis was performed on DNA isolated from peripheral WBCs. The patient's calcium and PTH concentrations were normal. Serum phosphorus concentrations ranged 5 to 6.7 mg/dL. 1,25-Hydroxy vitamin D levels were elevated. FGF23 C-terminal fragment concentrations were 53.79 RU/mL (reference interval 55 ± 50 RU/mL) and intact FGF23 concentrations were 11 pg/mL (reference interval 28 ± 2.2 pg/mL). Gene analysis showed no mutations in either FGF23 or GALNT3 genes. Reported cases of TC due to FGF23 and GALNT3 mutations have similar clinical and laboratory features. Our patient has most of the “classic” TC phenotypic features, but has normal circulating levels of C-terminal and intact FGF23, and no detected mutations of either the FGF23 or GALNT3 genes. Therefore, our case likely represents a new, yet undetermined, cause of TC.