High iFGF23 level despite hypophosphatemia is one of the clinical indicators to make diagnosis of XLH

Igaki, Junko; Yamada, Makoto; Yamazaki, Y.; Koto, Shinobu; Izawa, Masako; Ariyasu, Daisuke; Eri, Suzuki; Higuchi, Hisashi; Hasegawa, Yukihiro

doi:10.1507/endocrj.k10e-257

Cited by 23 publications

(14 citation statements)

References 25 publications

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“…As shown in ARHR2 patients, ENPP1 gene mutations are related to FGF23 elevation (Levy-Litan et al, 2010, Saito et al, 2011). In our patient, %TRP was relatively low under the condition of hypophosphatemia, and serum FGF23 level was high compared to those of normal subjects (10–50 pg/ml) (Yamazaki et al, 2002, Igaki et al, 2011). These biochemical data resembled the condition observed with X-linked hypophosphatemic rickets whose FGF23 levels are often elevated (Morey et al, 2011).…”

Section: Discussionmentioning

confidence: 41%

Hypophosphatemic rickets developed after treatment with etidronate disodium in a patient with generalized arterial calcification in infancy

et al. 2015

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Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was originally reported as a responsible gene for generalized arterial calcification in infancy (GACI). Though the prognosis of GACI patients is poor because of myocardial infarction and heart failure in relation to medial calcification of the coronary arteries, some patients rescued by bisphosphonate treatment have been reported. Recently, ENPP1 is also reported as responsible for autosomal recessive hypophosphatemic rickets type 2. We show here a boy with homozygous ENPP1 mutations diagnosed as having GACI in early infancy. After the diagnosis, he was treated with etidronate disodium (EHDP) in combination with antihypertensive drugs. The calcification of major arteries was diminished and disappeared by the age of eight months. He also showed mild hypophosphatemia (2.6–3.7 mg/dl) from the age of one year. After the treatment with EHDP for five years, he showed genu valgum with hypophosphatemia (2.6 mg/dl). He was diagnosed as having hypophosphatemic rickets at the age of seven years. The findings that hyper-mineralization of the arteries and hypo-mineralization of the bone observed in the same patient are noteworthy. ENPP1 could be regarded as a controller of the calcification of the whole body at least in part.

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Section: Discussionmentioning

confidence: 41%

Hypophosphatemic rickets developed after treatment with etidronate disodium in a patient with generalized arterial calcification in infancy

et al. 2015

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“…The native PHEX protein was reported to inactivate a phosphaturic factor, which is considered to be fibroblast growth factor 23 (FGF23) [21]. Circulatory FGF23 is elevated in most patients with XLH [22], and high level of intact FGF23 despite hypophosphatemia is a clinical indicator in XLH diagnosis [23]. While PHEX is expressed primarily in cells of bone lineage, the main protein effects on renal phosphate wasting and impaired vitamin D metabolism occur in the kidney.…”

Section: Discussionmentioning

confidence: 99%

Mutation in Phex Gene Predisposes BALB/c-PhexHyp-Duk/Y Mice to Otitis Media

Han

et al. 2012

PLoS ONE

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Genetic susceptibility underlying otitis media (OM) remains to be understood. We show in this study that mutation in Phex gene predisposes the BALB/c-PhexHyp-Duk/Y (abbreviated Hyp-Duk/Y) mice to OM, which occurs at post-natal day 21 (P21) with an average penetrance of 73%. The OM was identified by effusion in the middle ear cavity and/or thickening of middle ear mucosae, and was characterised by increase in goblet cells, deformity of epithelial cilia and higher expression of proliferating cell nuclear antigen (PCNA) in cells of the middle ear mucosae. Moreover, the transcription levels of Tlr2, Tlr4, Nfkb1, Ccl4, Il1b and Tnfα in the ears of the Hyp-Duk/Y mice at P35 were significantly upregulated, compared to those of the controls. Higher expression levels of TLR2, TLR4, NF-κB and TNF-α in the middle ears were demonstrated by immunohistochemistry (IHC). However, the OM in the mice was not prevented by azithromycin administration from gestational day 18 to P35. Further study showed that, in contrast to the low mRNA levels of Phex gene in the ears of the Hyp-Duk/Y mice, the mRNA level of Fgf23 was significantly elevated at P9, P14, P21 and P35. Meanwhile, mRNA levels of EP2 (PGE2 receptor), which expressed in the middle ear epithelia as demonstrated by IHC, were already increased at P14 even before the occurrence of OM, indicating that PGE2, an inflammatory mediator, is involved in the OM development in the mutants. Taking together, Phex mutation primarily up-regulates gene expression levels in FGF23 mediated pathways in the middle ears, resulting in cell proliferation and defence impairment at the mucosae and subsequently bacterial infection. The Hyp-Duk/Y mouse is a new genetic mouse model of OM.

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“…EDTA-plasma samples were used to determine FGF23 concentration by ELISA (C-FGF23: Immutopics, Inc., and I-FGF23 (22): Kainos, Tokyo, Japan) and intact PTH concentration by IRMA (Immulite, Siemens Healthcare Diagnostics, Camberley, Surrey, UK). Concentrations of C-FGF23 >125 RU/ml or I-FGF23 >52 pg/ml were considered elevated (23). LiHep-plasma samples were used for the other assays.…”

Section: Methodsmentioning

confidence: 99%

Predictors of intact and C-terminal fibroblast growth factor 23 in Gambian children

Braithwaite¹,

Jones²,

Assar³

et al. 2014

Endocrine Connections

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Elevated C-terminal fibroblast growth factor 23 (C-FGF23) concentrations have been reported in Gambian children with and without putative Ca-deficiency rickets. The aims of this study were to investigate whether i) elevated C-FGF23 concentrations in Gambian children persist long term; ii) they are associated with higher intact FGF23 concentrations (I-FGF23), poor iron status and shorter 25-hydroxyvitamin D half-life (25OHD-t1/2); and iii) the persistence and predictors of elevated FGF23 concentrations differ between children with and without a history of rickets. Children (8–16 years, n=64) with a history of rickets and a C-FGF23 concentration >125 RU/ml (bone deformity (BD), n=20) and local community children with a previously measured elevated C-FGF23 concentration (LC+, n=20) or a previously measured C-FGF23 concentration within the normal range (LC−, n=24) participated. BD children had no remaining signs of bone deformities. C-FGF23 concentration had normalised in BD children, but remained elevated in LC+ children. All the children had I-FGF23 concentration within the normal range, but I-FGF23 concentration was higher and iron status poorer in LC+ children. 1,25-dihydroxyvitamin D was the strongest negative predictor of I-FGF23 concentration (R2=18%; P=0.0006) and soluble transferrin receptor was the strongest positive predictor of C-FGF23 concentration (R2=33%; P≤0.0001). C-FGF23 and I-FGF23 concentrations were poorly correlated with each other (R2=5.3%; P=0.07). 25OHD-t1/2 was shorter in BD children than in LC− children (mean (s.d.): 24.5 (6.1) and 31.5 (11.5) days respectively; P=0.05). This study demonstrated that elevated C-FGF23 concentrations normalised over time in Gambian children with a history of rickets but not in local children, suggesting a different aetiology; that children with resolved rickets had a shorter 25OHD-t1/2, suggesting a long-standing increased expenditure of 25OHD, and that iron deficiency is a predictor of elevated C-FGF23 concentrations in both groups of Gambian children.

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High iFGF23 level despite hypophosphatemia is one of the clinical indicators to make diagnosis of XLH

Cited by 23 publications

References 25 publications

Hypophosphatemic rickets developed after treatment with etidronate disodium in a patient with generalized arterial calcification in infancy

Hypophosphatemic rickets developed after treatment with etidronate disodium in a patient with generalized arterial calcification in infancy

Mutation in Phex Gene Predisposes BALB/c-PhexHyp-Duk/Y Mice to Otitis Media

Predictors of intact and C-terminal fibroblast growth factor 23 in Gambian children

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