Two Case Reports of FGF23-Induced Hypophosphatemia in Childhood Biliary Atresia

Wasserman, Halley; Ikomi, Chijioke; Hafberg, Einar; Miethke, Alexander; Bove, Kevin E.; Backeljauw, Philippe

doi:10.1542/peds.2015-4453

Cited by 25 publications

(19 citation statements)

References 25 publications

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“…This outcome overlaps with more comprehensive qPCR-based tissue screens in mice, reporting that besides these tissues also spleen, lung, skeletal muscle, and stomach contain FGF23 mRNA ( 205 , 281 ). More detailed analyses of tissues and cultured cells by qPCR, immunoblotting, and immunohistochemistry, have confirmed and extended the findings of these screening studies, showing FGF23 expression in the heart ( 184 , 185 , 192 , 193 , 282 ), liver ( 283 , 284 ), kidney ( 190 , 285 – 287 ), spleen ( 216 , 288 , 289 ), brain ( 18 ), skeletal muscle ( 256 ), bone marrow ( 216 , 290 – 293 ), and macrophages ( 215 , 294 ). Also certain types of tumors have been shown to produce FGF23 ( 10 , 279 ).…”

Section: Discussionsupporting

confidence: 55%

FGF23 Actions on Target Tissues—With and Without Klotho

2018

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Fibroblast growth factor (FGF) 23 is a phosphaturic hormone whose physiologic actions on target tissues are mediated by FGF receptors (FGFR) and klotho, which functions as a co-receptor that increases the binding affinity of FGF23 for FGFRs. By stimulating FGFR/klotho complexes in the kidney and parathyroid gland, FGF23 reduces renal phosphate uptake and secretion of parathyroid hormone, respectively, thereby acting as a key regulator of phosphate metabolism. Recently, it has been shown that FGF23 can also target cell types that lack klotho. This unconventional signaling event occurs in an FGFR-dependent manner, but involves other downstream signaling pathways than in “classic” klotho-expressing target organs. It appears that klotho-independent signaling mechanisms are only activated in the presence of high FGF23 concentrations and result in pathologic cellular changes. Therefore, it has been postulated that massive elevations in circulating levels of FGF23, as found in patients with chronic kidney disease, contribute to associated pathologies by targeting cells and tissues that lack klotho. This includes the induction of cardiac hypertrophy and fibrosis, the elevation of inflammatory cytokine expression in the liver, and the inhibition of neutrophil recruitment. Here, we describe the signaling and cellular events that are caused by FGF23 in tissues lacking klotho, and we discuss FGF23’s potential role as a hormone with widespread pathologic actions. Since the soluble form of klotho can function as a circulating co-receptor for FGF23, we also discuss the potential inhibitory effects of soluble klotho on FGF23-mediated signaling which might—at least partially—underlie the pleiotropic tissue-protective functions of klotho.

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Section: Discussionsupporting

confidence: 55%

FGF23 Actions on Target Tissues—With and Without Klotho

2018

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“…Ectopic overexpression of FGF23 by hepatocytes was observed in 2 infants with endstage liver disease. 26 Additionally, serum FGF23 levels and the mRNA expression of FGF23 in the liver were significantly increased following the administration of lipopolysaccharides. 27 Basic research uncovered that FGF23 played a direct regulatory role in expression of Fetuin-A, an anti-inflammatory protein synthesized by the liver, which suggested a potential regulatory effect of FGF23 on inflammatory cytokines via the tumor necrosis factor-α/nuclear factorkappa B pathway.…”

Section: Discussionmentioning

confidence: 98%

<p>Association of Serum Fibroblast Growth Factor 23 Levels with the Presence and Severity of Hepatic Steatosis Is Independent of Sleep Duration in Patients with Diabetes</p>

Hu¹,

Yang²,

Wang³

et al. 2020

DMSO

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Purpose: Fibroblast growth factor (FGF) 23 is currently recognized to be involved in the occurrence and development of metabolic diseases. The present study aimed to investigate the association between serum FGF23 levels and hepatic steatosis, as well as the influence of sleep duration. Patients and Methods: The present study population was selected from patients with diagnosed diabetes hospitalized during February 2018 to April 2019. Serum FGF23 levels were assessed by two-side sandwich enzyme-linked immunosorbent assay. The presence and severity of hepatic steatosis were determined by controlled attenuation parameter (CAP). Hepatic steatosis was determined as CAP≥302 dB/m. Results: Serum FGF23 levels were significantly higher in individuals with hepatic steatosis than in those without hepatic steatosis (P=0.004). The present study population was divided into Q1-Q4 according to serum FGF23 quartiles. The risks of hepatic steatosis were increased more than 3 folds in Q2-Q4 (all P<0.01) compared to Q1. CAP showed an uptrend from Q1 to Q4 (P=0.005), even after adjustment for gender and age (P=0.001). Multivariate variance analyses showed significant differences in CAP among Q1-Q4 (P=0.008) and between individuals with short and long sleep duration (P=0.023), which were independent of each other. Serum FGF23 levels were positively associated with CAP independent of gender, age, total metabolic traits, and sleep duration (P=0.042). Conclusion: Serum FGF23 levels were independently and positively associated with the severity of hepatic steatosis. The associations of serum FGF23 levels and sleep duration with hepatic steatosis were independent of each other.

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“…2,15,24,27,28 A recent report of two cases of BA showed an association of elevated serum levels FGF23 and hypophosphatemia, which returned to normal levels after liver transplant. 29 Levels of FGF21 and FGF21 messenger RNA (mRNA) have been shown to be elevated in infants with BA. 30 MFS has been linked to mutation of RFX6 gene.…”

Section: Discussionmentioning

confidence: 99%

Achondroplasia and Biliary Atresia: A Rare Association and Review of Literature

Kylat

2017

J Pediatr Genet

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Achondroplasia (ACH) occurs in most cases as de novo mutations of the gene-encoding fibroblast growth factor receptor 3 (FGFR3). Biliary atresia (BA) is a progressive neonatal inflammatory and fibro-obliterative cholangiopathy affecting the extra- and intrahepatic biliary tree to varying degrees, and it results in obstruction to bile flow and cholestatic jaundice in neonates. BA is thought to be a multifactorial disease, genome association studies have shown abnormalities in susceptibility genes, and levels of fibroblast growth factor 21 (FGF21) and fibroblast growth factor 23 (FGF23) have been noted to be increased. These two conditions occurring in the same patient has never been reported before.

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Two Case Reports of FGF23-Induced Hypophosphatemia in Childhood Biliary Atresia

Cited by 25 publications

References 25 publications

FGF23 Actions on Target Tissues—With and Without Klotho

FGF23 Actions on Target Tissues—With and Without Klotho

<p>Association of Serum Fibroblast Growth Factor 23 Levels with the Presence and Severity of Hepatic Steatosis Is Independent of Sleep Duration in Patients with Diabetes</p>

Achondroplasia and Biliary Atresia: A Rare Association and Review of Literature

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