Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare and disabling disorder of
fibroblast growth factor 23 (FGF23) deficiency or resistance. The disorder is manifest by
hyperphosphatemia, inappropriately increased tubular reabsorption of
phosphate and 1,25-dihydroxy-Vitamin D, and ectopic calcifications. HFTC has been associated with autosomal recessive pathogenic variants in: (1) the gene encoding FGF23; (2) GALNT3, which encodes a
protein responsible for FGF23 glycosylation; and (3) KL, the gene encoding KLOTHO, a critical co-receptor for FGF23 signaling. An acquired autoimmune form of hyperphosphatemic
tumoral calcinosis has also been reported. Periarticular
tumoral calcinosis is the primary cause of disability in HFTC, leading to
pain, reduced range-of-motion, and impaired physical function. Inflammatory disease is also prominent, including diaphysitis with cortical
hyperostosis. Multiple treatment strategies have attempted to manage blood
phosphate, reduce
pain and
inflammation, and address calcifications and their complications. Unfortunately, efficacy data are limited to case reports and small cohorts, and no clearly effective
therapies have been identified. The purpose of this review is to provide a background on pathogenesis and clinical presentation in HFTC, discuss current approaches to clinical management, and outline critical areas of need for future research.