Differences in Hepatic Phenotype Between Hemochromatosis Patients With HFE C282Y Homozygosity and Other HFE Genotypes

Cheng, Raymond; Barton, James C.; Morrison, Elizabeth D.; Phatak, Pradyumna D.; Krawitt, Edward L.; Gordon, Stuart C.; Kowdley, Kris V.

doi:10.1097/mcg.0b013e3181919a33

Cited by 39 publications

(27 citation statements)

References 15 publications

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“…It is well-known that the liver IO in HH produced by the C282Y/C282Y mutation is higher than that produced by other mutations, such as C282Y/H63D or H63D/H63D (6,15). The causative role of C282Y/H63D and H63D/H63D mutations in HH or IO has been demonstrated, but with less penetrance and a considerable phenotypic variability (6,15). The absence of C282Y homozygotic patients in our study may have been why no differences were detected.…”

Section: Discussioncontrasting

confidence: 45%

“…One of the problems in this study is that there were no C282Y/C282Y patients in the series. It is well-known that the liver IO in HH produced by the C282Y/C282Y mutation is higher than that produced by other mutations, such as C282Y/H63D or H63D/H63D (6,15). The causative role of C282Y/H63D and H63D/H63D mutations in HH or IO has been demonstrated, but with less penetrance and a considerable phenotypic variability (6,15).…”

Section: Discussionmentioning

confidence: 99%

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Liver Iron Concentration in Patients Referred to a Secondary Hospital for Hyperferritinemia: Analysis of the Different Groups According to HFE Mutations and the Transferrin Saturation Index

Castiella¹,

Zapata²,

Zubiaurre³

et al. 2017

Hepat Mon

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Background: Olynyk et al. studied the liver iron concentration (LIC) by MRI of 52 consecutive patients of northern European origin who were referred to a tertiary hospital for hyperferritinemia (HF). They described three groups according to HFE mutations and the transferrin saturation index (TSI) (group A: no predisposing mutations (PM) for hereditary hemochromatosis (HH) and TSI > 45 %, group B: PM for HH and TSI > 45 %; group C: no PM for HH and normal TSI). In the Basque country, HH predisposing mutations differ, with prevalence of the H63D/H63D mutation.

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Section: Discussioncontrasting

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Liver Iron Concentration in Patients Referred to a Secondary Hospital for Hyperferritinemia: Analysis of the Different Groups According to HFE Mutations and the Transferrin Saturation Index

Castiella¹,

Zapata²,

Zubiaurre³

et al. 2017

Hepat Mon

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“…2,104 High ferritin levels have also been found to be closely associated with the development of hepatic fibrosis in Cys282Tyr homozygous or Cys282Tyr/His63Asp heterozygous patients of advanced age. 118 Conclusions A diagnosis of hereditary hemochromatosis can easily be based on the characteristically raised concentrations of circulating markers of iron metabolism in the blood, followed by genetic testing and, if confirmed, by screen ing of firstdegree relatives. [1][2][3][4] Early initiation of therapy can avoid tissue damage and organ failure as a conse quence of progressive iron accumulation.…”

Section: Infections and Inflammationmentioning

confidence: 99%

Genetic mechanisms and modifying factors in hereditary hemochromatosis

Weiss

2009

Nat Rev Gastroenterol Hepatol

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Primary iron overload is one of the most common inherited diseases worldwide. Several genetic mutations underlie the various forms of the disease, which have similar pathophysiological profiles but distinct clinical presentations. Patients with hereditary hemochromatosis absorb too much iron from the diet, which accumulates over time within parenchymal cells. This accumulation leads to eventual organ failure as a consequence of iron-mediated formation of free radicals. The mechanism underlying this excessive absorption of iron is a sensing defect caused by the reduced formation of hepcidin, the master regulator of iron homeostasis, as a consequence of mutations in the genes encoding several membrane-bound signaling molecules present on hepatocytes. A considerable number of carriers of these specific genetic mutations, however, do not develop iron overload, indicating that additional genetic and environmental factors modify the severity and clinical penetrance of disease. In affected patients, early initiation of treatment by phlebotomy can prevent organ damage. Genetic screening of first-degree relatives can be also used to identify individuals at risk. Our expanding knowledge of the regulation of iron metabolism and the role of factors that modify the severity of the disease may lead to the design of new and improved treatments.

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“…Large population studies have shown that both the compound heterozygous and homozygous H63D genotypes have much lower penetrance than the C282Y homozygous genotype (1,2). In the haemochromatosis phenotype, hyper-ferritinaemia, transferrin saturation (1,5) and increased hepatic iron concentration (6) are associated with H63D homo-or hetero-zygosity as observed with C282Y homozygotes or C282/H63D.…”

mentioning

confidence: 92%

Distribution and Quantitation of Skin Iron in Primary Haemochromatosis: Correlation with Total Body Iron Stores in Patients Undergoing Phlebotomy

Pinheiro¹,

Silva²,

Fleming³

et al. 2014

Acta Derm Venerol

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Measurement of the concentration of iron in the skin, if correlated with total body iron stores, may enable better informed decisions on when to initiate, change or stop therapy in hereditary heamochromatosis. Naïve haemochromatosis patients with iron overload and with C282Y and/or H63D HFE mutations were evaluated at the following time-points: disease diagnosis, end of the therapy programme, and 6 months after the end of therapy. The distribution and concentration of iron in the skin were assessed by quantitative nuclear microscopy methods, in parallel with serum and plasma iron concentration. Iron content in the liver was determined by nuclear magnetic resonance. Iron accumulated in the epidermis; its concentration increased from outer to inner layers, being maximal in the basal layer (7.33 ± 0.98 µmol/g). At all 3 time-points, most of the iron was associated with the extracellular space. During the phlebotomy programme the iron content of the skin and the liver decreased by a factor of 2. These data suggest that measurements of iron concentration in the epidermis, which is a readily accessible tissue, reflect iron overload in the liver.

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Differences in Hepatic Phenotype Between Hemochromatosis Patients With HFE C282Y Homozygosity and Other HFE Genotypes

Cited by 39 publications

References 15 publications

Liver Iron Concentration in Patients Referred to a Secondary Hospital for Hyperferritinemia: Analysis of the Different Groups According to HFE Mutations and the Transferrin Saturation Index

Liver Iron Concentration in Patients Referred to a Secondary Hospital for Hyperferritinemia: Analysis of the Different Groups According to HFE Mutations and the Transferrin Saturation Index

Genetic mechanisms and modifying factors in hereditary hemochromatosis

Distribution and Quantitation of Skin Iron in Primary Haemochromatosis: Correlation with Total Body Iron Stores in Patients Undergoing Phlebotomy

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