Iron storage disease in <scp>A</scp>sia‐<scp>P</scp>acific populations: The importance of non‐<scp><i>HFE</i></scp> mutations

McDonald, Cameron; Wallace, Daniel F.; Crawford, Darrell H. G.; Subramaniam, V. Nathan

doi:10.1111/jgh.12222

Cited by 44 publications

(50 citation statements)

References 72 publications

(131 reference statements)

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“…66 In type 1 HH at diagnosis, serum hepcidin levels are typically in the low to normal range and inappropriate for the degree of IO (manifesting as a low hepcidin-to-ferritin ratio). 41 Hepcidin is further suppressed after normalization of iron stores by phlebotomies 15,41 and shows a blunted response to oral iron.…”

Section: Diagnosis Of Io Disordersmentioning

confidence: 99%

Hepcidin in the diagnosis of iron disorders

Girelli

Nemeth

Swinkels

2016

Blood

346

291

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The discovery of the iron-regulatory hormone hepcidin in 2001 has revolutionized our understanding of iron disorders, and its measurement should advance diagnosis/treatment of these conditions. Although several assays have been developed, a gold standard is still lacking, and efforts toward harmonization are ongoing. Nevertheless, promising applications can already be glimpsed, ranging from the use of hepcidin levels for diagnosing iron-refractory iron deficiency anemia to global health applications such as guiding safe iron supplementation in developing countries with high infection burden.

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Section: Diagnosis Of Io Disordersmentioning

confidence: 99%

Hepcidin in the diagnosis of iron disorders

Girelli

Nemeth

Swinkels

2016

Blood

346

291

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“…20 In Asian countries the majority of HH cases are related to non-HFE genes. 21 Despite the wealth of publications on the various causes of non-HFE HH, to our knowledge no systematic study has attempted to estimate the prevalence of these atypical forms of iron overload. The frequency of individual non-HFE mutations among the general population have only been estimated to be rare; no other quantitative measure of their frequency is available.…”

Section: Discussionmentioning

confidence: 99%

The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data

Wallace

Subramaniam

2016

Genetics in Medicine

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Purpose:The prevalence of HFE-related hereditary hemochromatosis (HH) among European populations has been well studied. There are no prevalence data for atypical forms of HH caused by mutations in HFE2, HAMP, TFR2, or SLC40A1. The purpose of this study was to estimate the population prevalence of these non-HFE forms of HH.Methods: A list of HH pathogenic variants in publically available next-generation sequence (NGS) databases was compiled and allele frequencies were determined.Results: Of 161 variants previously associated with HH, 43 were represented among the NGS data sets; an additional 40 unreported functional variants also were identified. The predicted prevalence of HFE HH and the p.Cys282Tyr mutation closely matched previous estimates from similar populations. Of the non-HFE forms of iron overload, TFR2-, HFE2-, and HAMP-related forms are predicted to be rare, with pathogenic allele frequencies in the range of 0.00007 to 0.0005. Significantly, SLC40A1 variants that have been previously associated with autosomal-dominant ferroportin disease were identified in several populations (pathogenic allele frequency 0.0004), being most prevalent among Africans. Conclusion:We have, for the first time, estimated the population prevalence of non-HFE HH. This methodology could be applied to estimate the population prevalence of a wide variety of genetic disorders.

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“…Types I-III are linked to altered or reduced expression of hepcidin [11,25,27], whereas type IV results from reduced iron export [1,28]. Mutations in HFE, HJV, HAMP, TFR2 and SLC40A1 have been linked to the various types of hemochromatosis [11,25,29], each displaying different onsets, severities and prevalences [2,4,9,25,27,[29][30][31][32][33] (Table 1).…”

Section: Genetics and Penetrancementioning

confidence: 97%

“…The C282Y substitution resulting from a missense mutation in HFE is the most common cause of hereditary hemochromatosis in Caucasian populations [25,30], with up to 90 % of hemochromatosis cases being associated with homozygosity for the mutation [9,25,30,34]. However, there is significant variance in C282Y incidence with ethnic diversity [1,29,35,36].…”

Section: Hfe-associated Hereditary Hemochromatosismentioning

confidence: 98%

“…The genetic bases for hemochromatosis can be divided principally into HFE gene mutations and non-HFE mutations [25]. The presence of non-HFE hemochromatosis was elucidated by Zarrilli et al [26] when a purely clinical diagnosis of hemochromatosis yielded a higher incidence rate when compared with the genetic diagnosis based on the HFE genotype.…”

Section: Genetics and Penetrancementioning

confidence: 99%

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Recent advances in hemochromatosis: a 2015 update

2015

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This review focuses on iron metabolism, the genetics of hemochromatosis, current treatment protocols and various screening methods. Even though the most common form of hereditary hemochromatosis, C282Y gene mutations in the HFE gene, has been extensively studied, novel mutations in both HFE and non-HFE genes have been implicated in this disease. These have important implications for the Asia-Pacific region. In overload, deposition of iron in various body tissues leads to toxic damage. Patients commonly present with non-specific symptoms of malaise and lethargy. Biochemical, imaging and genetic testing can be carried out to confirm diagnosis. Venesection forms the mainstay of treatment and at present cascade screening of affected families is recommended over population-level screening.

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Iron storage disease in Asia‐Pacific populations: The importance of non‐HFE mutations

Cited by 44 publications

References 72 publications

Hepcidin in the diagnosis of iron disorders

Hepcidin in the diagnosis of iron disorders

The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data

Recent advances in hemochromatosis: a 2015 update

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