Autoimmune hyperphosphatemic tumoral calcinosis

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

doi:10.1530/boneabs.6.oc20

Cited by 15 publications

(35 citation statements)

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“…is a rare disorder of phosphate metabolism caused by mutations in genes related to Fibroblast Growth Factor-23 (FGF23), which include FGF23 itself, an FGF23glycosylating enzyme, N-acetylgalactosaminyltransfer ase 3 (GALNT3), and the FGF23 co-receptor α-Klotho (αKL) (1). The altered gene function decreases FGF23 synthesis or activity and causes increased renal tubular reabsorption of phosphate, thereby increasing blood calcium-phosphate product, which leads to predisposition for soft-tissue calcification (2).…”

Section: Hyperphosphatemic Familial Tumoral Calcinosis (Hftc)mentioning

confidence: 99%

“…The most common manifestation of HFTC is calcinosis cutis, which appears clinically as firm, otherwise asymptomatic, white, yellowish or flesh-colored papules, plaques, or nodules. The clinical course is often associated with excretion of chalky material, pain, itching, ulceration, or infection of the lesions (1).…”

Section: Hyperphosphatemic Familial Tumoral Calcinosis (Hftc)mentioning

confidence: 99%

“…Only about 75 patients of genetically confirmed HTFC have been reported (1). The majority (about 80%) have mutations in the GALNT3 gene followed by the FGF23 gene (about 20%) and the KL gene (1).…”

Section: Hyperphosphatemic Familial Tumoral Calcinosis (Hftc)mentioning

confidence: 99%

“…Therefore, the FGF23 protein is readily cleaved into biologically inactive N-terminal and C-terminal fragments (c-FGF23). The loss of FGF23 activity leads to hyperphosphatemia typical of HFTC (1). The circulating concentrations of c-FGF23 are increased whereas the intact FGF23 (i-FGF23) remains low or inappropriately normal for the level of hyperphosphatemia (1).…”

Section: Hyperphosphatemic Familial Tumoral Calcinosis (Hftc)mentioning

confidence: 99%

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A novel homozygous variant in exon 10 of the <i>GALNT3</i> gene causing hyperphosphatemic familial tumoral calcinosis in a family from North India

Dayal

Gupta

Kumar

et al. 2021

IRDR

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Section: Hyperphosphatemic Familial Tumoral Calcinosis (Hftc)mentioning

confidence: 99%

Section: Hyperphosphatemic Familial Tumoral Calcinosis (Hftc)mentioning

confidence: 99%

Section: Hyperphosphatemic Familial Tumoral Calcinosis (Hftc)mentioning

confidence: 99%

Section: Hyperphosphatemic Familial Tumoral Calcinosis (Hftc)mentioning

confidence: 99%

See 2 more Smart Citations

A novel homozygous variant in exon 10 of the <i>GALNT3</i> gene causing hyperphosphatemic familial tumoral calcinosis in a family from North India

Dayal

Gupta

Kumar

et al. 2021

IRDR

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“…As PTH has a significant influence on promoting phosphaturia, loss of PTH caused by hypoparathyroidism or peripheral resistance to its action (pseudohypoparathyroidism) can produce elevated phosphate levels [21]. Familial tumoral calcinosis, an autosomal recessive disease caused by a mutation in the GALNT3, FGF23 or klotho gene, is characterised by resistance to FGF23, which also leads to hyperphosphataemia [40]. Increased levels of growth hormone and insulin-like growth factor 1 (Igf-1) seen in acromegaly stimulate phosphate reabsorption in the PCT.…”

Section: Hyperphosphataemiamentioning

confidence: 99%

Calcium, Phosphate and Magnesium Disorders

Heron¹

2019

Fluid and Electrolyte Disorders

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Calcium, phosphate and magnesium are essential for human function and life. Each electrolyte is readily found in the human diet, and homeostasis is tightly regulated by the intestine, kidney and bone as well as other critical hormones, receptors and transporters. Disturbance to this balance can result in symptomatic disease and life-threatening manifestations. Calcium and phosphate are particularly co-dependent with disruption to the balance of one often influencing the other. It is important that clinicians have a thorough understanding of the mechanisms underplaying the homeostasis of each electrolyte as they have implications for prevention and management of disease. This chapter aims to outline the importance of calcium, phosphate and magnesium; the regulation of each electrolyte and the consequences of imbalance.

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A Cross‐Sectional Cohort Study of the Effects of FGF23 Deficiency and Hyperphosphatemia on Dental Structures in Hyperphosphatemic Familial Tumoral Calcinosis

et al. 2021

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Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder caused by mutations in FGF23, GALNT3, KLOTHO, or FGF23 autoantibodies. Prominent features include high blood phosphate and calcific masses, usually adjacent to large joints. Dental defects have been reported, but not systematically described. Seventeen patients with HFTC followed at the National Institutes of Health underwent detailed clinical, biochemical, molecular, and dental analyses. Studies of teeth included intraoral photos and radiographs, high‐resolution μCT, histology, and scanning electron microscopy (SEM). A scoring system was developed to assess the severity of tooth phenotype. Pulp calcification was found in 13 of 14 evaluable patients. Short roots and midroot bulges with apical thinning were present in 12 of 13 patients. Premolars were most severely affected. μCT analyses of five HFTC teeth revealed that pulp density increased sevenfold, whereas the pulp volume decreased sevenfold in permanent HFTC teeth compared with age‐ and tooth‐matched control teeth. Histology revealed loss of the polarized odontoblast cell layer and an obliterated pulp cavity that was filled with calcified material. The SEM showed altered pulp and cementum structures, without differences in enamel or dentin structures, when compared with control teeth. This study defines the spectrum and confirms the high penetrance of dental features in HFTC. The phenotypes appear to be independent of genetic/molecular etiology, suggesting hyperphosphatemia or FGF23 deficiency may be the pathomechanistic driver, with prominent effects on root and pulp structures, consistent with a role of phosphate and/or FGF23 in tooth development. Given the early appearance and high penetrance, cognizance of HFTC‐related features may allow for earlier diagnosis and treatment. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

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Autoimmune hyperphosphatemic tumoral calcinosis

Cited by 15 publications

References 0 publications

A novel homozygous variant in exon 10 of the <i>GALNT3</i> gene causing hyperphosphatemic familial tumoral calcinosis in a family from North India

A novel homozygous variant in exon 10 of the <i>GALNT3</i> gene causing hyperphosphatemic familial tumoral calcinosis in a family from North India

Calcium, Phosphate and Magnesium Disorders

A Cross‐Sectional Cohort Study of the Effects of FGF23 Deficiency and Hyperphosphatemia on Dental Structures in Hyperphosphatemic Familial Tumoral Calcinosis

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