Serum hepcidin measured by immunochemical and mass-spectrometric methods and their correlation with iron status indicators in healthy children aged 0.5–3 y

Uijterschout, Lieke; Swinkels, Dorine W.; Domellöf, Magnus; Lagerqvist, Carina; Hudig, Cisca; Tjalsma, Harrold; Vos, Rimke C.; Goudoever, Johannes B. van; Brus, F

doi:10.1038/pr.2014.109

Cited by 27 publications

(19 citation statements)

References 32 publications

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“…The median reference level of serum hepcidin‐25 is 4.5 nM for men (p 2.5–p 97.5 ≤ 0.5–14.7 nM), 2.0 nM for premenopausal women (p 2.5–p 97.5 = 0.1–12.3 nM) and 4.9 nM for postmenopausal women (p 2.5–p 97.5 = 0.2–15.6 nM). The reference level of serum hepcidin‐25 for children aged 0.5–3 years is 3.6 nM (p 2.5–p.97.5 = 0.94–12.2) . For children >3 years no reference ranges are available until now, so for this group we recommend using those of premenopausal women.…”

Section: Methodsmentioning

confidence: 99%

Iron refractory iron deficiency anemia: a heterogeneous disease that is not always iron refractory

et al. 2016

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TMPRSS6 variants that affect protein function result in impaired matriptase-2 function and consequently uninhibited hepcidin production, leading to iron refractory iron deficiency anemia (IRIDA). This disease is characterized by microcytic, hypochromic anemia and serum hepcidin values that are inappropriately high for body iron levels. Much is still unknown about its pathophysiology, genotype-phenotype correlation, and optimal clinical management. We describe 14 different TMPRSS6 variants, of which 9 are novel, in 21 phenotypically affected IRIDA patients from 20 families living in the Netherlands; 16 out of 21 patients were female. In 7 out of 21 cases DNA sequencing and multiplex ligation dependent probe amplification demonstrated only heterozygous TMPRSS6 variants. The age at presentation, disease severity, and response to iron supplementation were highly variable, even for patients and relatives with similar TMPRSS6 genotypes. Mono-allelic IRIDA patients had a milder phenotype with respect to hemoglobin and MCV and presented significantly later in life with anemia than bi-allelic patients. Transferrin saturation (TSAT)/hepcidin ratios were lower in IRIDA probands than in healthy relatives. Most patients required parenteral iron. Genotype alone was not predictive for the response to oral iron. We conclude that IRIDA is a genotypically and phenotypically heterogeneous disease. The high proportion of female patients and the discrepancy between phenotypes of probands and relatives with the same genotype, suggest a complex interplay between genetic and acquired factors in the pathogenesis of IRIDA. In the absence of inflammation, the TSAT/hepcidin ratio is a promising diagnostic tool, even after iron supplementation has been given.Am. J. Hematol. 91:E482-E490,

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Section: Methodsmentioning

confidence: 99%

Iron refractory iron deficiency anemia: a heterogeneous disease that is not always iron refractory

et al. 2016

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“…20 Implementation of measurement of serum hepcidin levels in clinical pediatrics is hampered by the lack of standardized reference values for healthy children from different age groups, relative to iron status. [24][25][26] Available studies concern either small series with limited age groups or series including children with (anemia of) inflammation. 16,[27][28][29][30][31] As a first step to the implementation of serum hepcidin measurements in pediatric clinical practice, we established age-and sex-specific (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Standardized serum hepcidin values in Dutch children: Set point relative to body iron changes during childhood

Donker

Galesloot²,

Laarakkers

et al. 2019

Pediatric Blood & Cancer

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Background: Use of serum hepcidin measurements in pediatrics would benefit from standardized age-and sex-specific reference ranges in children, in order to enable the establishment of clinical decision limits that are universally applicable. Procedure:We measured serum hepcidin-25 levels in 266 healthy Dutch children aged 0.3-17 years, using an isotope dilution mass spectrometry assay, standardized with our commutable secondary reference material (RM), assigned by a candidate primary RM. Results:We constructed age-and sex-specific values for serum hepcidin and its ratio with ferritin and transferrin saturation (TSAT). Serum hepcidin levels and hepcidin/ferritin and TSAT/hepcidin ratios were similar for both sexes. Serum hepcidin and hepcidin/ferritin ratio substantially declined after the age of 12 years and TSAT/hepcidin ratio gradually increased with increasing age. Serum hepcidin values for Dutch children <12 years (n = 170) and >12 years (n = 96) were 1.9 nmol/L (median); 0.1-13.1 nmol/L (p2.5-p97.5) and 0.9 nmol/L; 0.0-9.1 nmol/L, respectively. Serum ferritin was the most significant correlate of serum hepcidin in our study population, explaining 15.1% and 7.9% of variance in males and females, respectively. Multivariable linear regression analysis including age, blood sampling time, iron parameters, ALT, CRP, and body mass index as independent variables showed a statistically significant negative association between age as a dichotomous variable (≤12 vs >12 years) and log-transformed serum hepcidin levels in both sexes. Conclusions:We demonstrate that serum hepcidin relative to indicators of body iron is age dependent in children, suggesting that the set point of serum hepcidin relative to stored and circulating iron changes during childhood. K E Y W O R D Schild, ferritin, hepcidin, pediatric reference ranges, transferrin saturation

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“…Serum hepcidin reference ranges have been estimated for the adult population . Paediatric reference ranges were also published . However, further standardisation of the methodology is necessary.…”

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“…13,14 Paediatric reference ranges were also published. [15][16][17] However, further standardisation of the methodology is necessary.…”

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Hepcidin in newly diagnosed inflammatory bowel disease in children

Karásková

Volejnikova

Holub

et al. 2018

J Paediatrics Child Health

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Serum hepcidin measured by immunochemical and mass-spectrometric methods and their correlation with iron status indicators in healthy children aged 0.5–3 y

Cited by 27 publications

References 32 publications

Iron refractory iron deficiency anemia: a heterogeneous disease that is not always iron refractory

Iron refractory iron deficiency anemia: a heterogeneous disease that is not always iron refractory

Standardized serum hepcidin values in Dutch children: Set point relative to body iron changes during childhood

Hepcidin in newly diagnosed inflammatory bowel disease in children

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