Abstract
BackgroundHereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism in Northern European populations. The discovery of a candidate gene in 1996 (HFE), and of its main mutation (C282Y), has radically altered the way to diagnose this disease. The aim of this study was to assess the impact of the HFE gene discovery on the clinical presentation and epidemiology of HH.MethodsWe studied our cohort of 415 patients homozygous for the C282Y allele and included in a phlebotomy program in a blood centre in western Brittany, France.ResultsIn this cohort, 56.9% of the patients were male and 21.9% began their phlebotomy program before the implementation of the genetic test. A significant decrease in the sex ratio was noticed following implementation of this DNA test, from 3.79 to 1.03 (p < 10-5), meaning that the proportion of diagnosed females relatives to males greatly increased. The profile of HH patients at diagnosis changed after the DNA test became available. Serum ferritin and iron values were lower and there was a reduced frequency of clinical signs displayed at diagnosis, particularly skin pigmentation (20.1 vs. 40.4%, OR = 0.37, p < 0.001) and hepatomegaly (11.0 vs. 22.7%, OR = 0.42, p = 0.006). In contrast, fatigue became a more common symptom at diagnosis (68.0 vs. 51.2%, OR = 2.03, p = 0.004).ConclusionThis study highlights the importance of the HFE gene discovery, which has simplified the diagnosis of HH and modified its clinical presentation and epidemiology. This study precisely measures these changes. Enhanced diagnosis of HFE-related HH at an early stage and implementation of phlebotomy treatment are anticipated to maintain normal life expectancy for these patients.
Highlights
Hereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism in Northern European populations
Hereditary hemochromatosis (HH) is a common genetic disorder of iron metabolism that is usually inherited in an autosomal recessive pattern and associated with missense mutations in the HFE gene
This pathology displays a large genetic heterogeneity because several other types of hemochromatosis, associated with different genes and patterns of inheritance, have been reported [1]: HH type 2B is a juvenile form linked to the HAMP gene [2,3,4], HH type 3 is linked to the TfR2 gene [5,6,7], HH type 4 is linked to the SLC11A3 gene [8,9]. and HH type 5 is linked to a gene encoding subunit H of ferritin [10]
Summary
Hereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism in Northern European populations. The main form of HH (i.e. type I which is linked to the HFE gene) occurs predominantly in Northern European populations, with a prevalence of approximately 3 to 8 in 1000 [12,13,14,15,16] It is characterised by excessive iron absorption, which progressively leads to the destruction of tissues in different organs of the body. The clinical picture may include at an early stage, non-specific symptoms such as persistent fatigue and arthralgias, and at a later stage, clinical signs such as skin pigmentation, hepatomegaly, arthropathy, cardiomyopathy, diabetes and cirrhosis [20,21,22] This clinical expression occurs more frequently in males than in females (sex ratio of 3:1) [23]
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