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Diagnosis of Hemochromatosis type 1- HFE gene

Pictogramme horloge Laurence Strompf Pictogramme horloge October 2014

Haemochromatosis is a hereditary disease inherited in an autosomal recessive pattern with variable penetrance; it is linked to the HFE gene. It is the most common genetic disease in the Caucasian population, particularly in individuals of Nordic and/or Celtic origin (prevalence 1/260).
The disease is associated with a characteristic excess of serum iron, which is deposited in the parenchymal cells of many tissues and organs, thus explaining the clinical symptoms.
The disease manifests itself in men between the age of 30 and 40 years, and somewhat later in women due to relative protection as the result of menstrual bleeding and pregnancy.

The clinical picture is varied and includes asthenia, melanoderma, chronic joint pain, and endocrine, hepatic and cardiovascular disorders. The three most common sequence variants of the HFE gene researched within the context of iron balance disturbance are: p.Cys282Tyr (C282Y), p.His63Asp (H63D) and p.Ser65Cys (S65C).
However, genetic diagnosis is based solely on the detection of homozygosity for C282Y, which accounts for approximately 80% of clinically diagnosed patients.
Heterozygous combinations of C282Y and H63D or S65C and H63D homozygosity are only considered to have an impact on iron balance and/or on clinical symptoms in the presence of comorbidities.

Haemochromatosis screening may be indicated:

In individuals:

  • If transferrin saturation values are > 45% and after exclusion of all other aetiologies that could cause this increase
  • Following a targeted assessment that revealed clinical signs, biological results or histology findings suggestive of haemochromatosis

In a context of family history:

In a subject who is a first-degree relative of a person carrying the mutation, with the exception of minor subjects and mothers who are post-menopausal or who no longer wish to have children.

In the event of altered iron balance with hyperferritinaemia but transferrin saturation <45%, it is first necessary to investigate an alternative cause: metabolic syndrome, inflammation, cell lysis, excessive alcohol consumption, etc.

Legal framework

For any test involving constitutional genetics (molecular genetics and cytogenetics), the sample must be accompanied by the following documents:

  • Medical prescription
  • Confirmation of genetic counselling completed by the prescribing physician
  • Informed consent signed by the adult patient


Decree No. 2008-321 of 4 April 2008, Order of 27 May 2013 defining the rules of good practice applicable to the investigation of the genetic characteristics of a person for medical purposes, Article L.1131-2 CSP [French Code of Public Health]


European Association for the Study of the Liver. EASL clinical practice guidelines for HFE hemochromatosis. Journal of Hepatology 2010; 53(1): 3–22. Deugnier Y, Bardou-Jacquet E, Ropert M, et al. Prise en charge actuelle des hémochromatoses. Feuillets de Biologie 2012; 309: 17-23. Sogni P, Buffet C. Démarche clinique devant une hyperferritinémie. La Presse médicale 2013 ; 42(4): 405-10.

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