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Hemochromatosis type 1

Orpha number ORPHA139498
Synonym(s) C282Y/C282Y hemochromatosis
Classic hemochromatosis
HFE-related hemochromatosis
Prevalence >1 / 1000
Inheritance
  • Autosomal recessive
Age of onset Adulthood
ICD-10
  • E83.1
OMIM
UMLS -
MeSH -
MedDRA -
SNOMED CT
  • 399144008
  • 399187006

Summary

Hemochromatosis type 1 (classic) is the most common form of hereditary hemochromatosis (HH), a group of diseases characterized by excessive tissue iron deposition.

HH type 1 is exclusively and commonly found in Caucasian populations with a prevalence of the genetic predisposition of 1/200-1/1,000 but, due to its low penetrance and variable phenotypic expression, severe forms of the disease are rare. Men are clinically more affected than women.

Age of clinical onset varies between 30 and 50 years old. Hemochromatosis type 1 causes chronic fatigue, bronzed skin pigmentation and tissue damage in the liver, pancreas, joints, bone, endocrine glands, heart, which result in various complications in adulthood including liver fibrosis (cirrhosis with a risk of hepatocellular carcinoma), diabetes mellitus, arthropathy, osteoporosis, hypogonadotropic hypogonadism, and cardiac failure. Biochemical abnormalities include elevated serum iron, transferrin saturation, serum ferritin.

The disease is due to a major mutation in the HFE gene localized on chromosome 6 (the C282Y mutation). Visceral iron excess is related to hypohepcidinemia which leads to increased serum iron and transferrin saturation through both enhanced intestinal iron absorption and increased iron release from the spleen.

Diagnosis is based on biochemical testing using serum transferrin saturation and serum ferritin, and on imaging to diagnose visceral iron overload (magnetic resonance imaging). Molecular genetic blood testing allows the diagnosis to be established in a non invasive way (i.e. without a liver biopsy) by showing C282Y homozygosity.

Differential diagnosis includes i) for hyperferritinemia: alcoholism, polymetabolic syndrome, and inflammatory conditions, ii) for visceral iron overload: hemochromatosis type 3 and type 4 (in its form B) (see these terms), and post-transfusional iron overload in the case of hematological diseases such as myelodysplastic syndromes, thalassemia major, sickle cell disease and other rare anemias (see these terms).

Transmission is autosomal recessive. Genetic counseling should be offered to affected families, informing them of the risk of inheriting the disease-causing mutation.

Patients are treated by repeated phlebotomies that are initially performed on a weekly basis until the ferritin level reaches 50 microg/l, after which they are performed every 1-3 months.

Hemochromatosis type 1 has a very good prognosis, and patients have a normal life expectancy when treated early, before the development of complications like cirrhosis, liver cancer, insulin-dependent diabetes, and cardiomyopathy.

Expert reviewer(s)

  • Pr Pierre BRISSOT

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Detailed information

Guidance for genetic testing
  • EN (2010,pdf)
Article for general public
  • FR (2006,pdf)
Clinical genetics review
  • EN (2012)
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The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.