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Autoimmune hyperphosphatemic tumoral calcinosis in a patient with FGF23 autoantibodies
Mary Scott Roberts, … , Michael T. Collins, Rachel I. Gafni
Mary Scott Roberts, … , Michael T. Collins, Rachel I. Gafni
Published September 18, 2018
Citation Information: J Clin Invest. 2018;128(12):5368-5373. https://doi.org/10.1172/JCI122004.
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Concise Communication Bone Biology Endocrinology

Autoimmune hyperphosphatemic tumoral calcinosis in a patient with FGF23 autoantibodies

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Abstract

Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition to the classical clinical and biochemical features of hyperphosphatemic tumoral calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23 levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or FGF receptor 1 (FGFR1) were identified. He subsequently developed type 1 diabetes mellitus, which raised the possibility of an autoimmune cause for hyperphosphatemic tumoral calcinosis. Luciferase immunoprecipitation systems revealed markedly elevated FGF23 autoantibodies without detectable FGFR1 or Klotho autoantibodies. Using an in vitro FGF23 functional assay, we found that the FGF23 autoantibodies in the patient’s plasma blocked downstream signaling via the MAPK/ERK signaling pathway in a dose-dependent manner. Thus, this report describes the first case, to our knowledge, of autoimmune hyperphosphatemic tumoral calcinosis with pathogenic autoantibodies targeting FGF23. Identification of this pathophysiology extends the etiologic spectrum of hyperphosphatemic tumoral calcinosis and suggests that immunomodulatory therapy may be an effective treatment.

Authors

Mary Scott Roberts, Peter D. Burbelo, Daniela Egli-Spichtig, Farzana Perwad, Christopher J. Romero, Shoji Ichikawa, Emily Farrow, Michael J. Econs, Lori C. Guthrie, Michael T. Collins, Rachel I. Gafni

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Figure 1

Clinical presentation and radiographs of patient with tumoral calcinosis.

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Clinical presentation and radiographs of patient with tumoral calcinosis...
(A) Tumoral calcinosis (arrows) of the lateral right hip at initial presentation to the NIH at 7 years, 3 months old. (B) Radiograph of the lesion revealed a soft tissue mass with amorphous calcifications around the right greater trochanter consistent with tumoral calcinosis. Repeat evaluation 9 months after initial presentation while on phosphate-lowering medications (sevelamer and acetazolamide) and a low-phosphate diet showed decrease in the size of the tumoral calcinosis (arrows) on physical exam (C) and repeat radiograph (D).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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