From the Guidelines
Hemochromatosis is a genetic disease characterized by increased transferrin saturation and liver iron overload, in the absence of anemia and/or reticulocytosis, caused by a deficiency or impairment in hepcidin synthesis or function due to pathogenic variants in genes regulating hepcidin production or function.
Key Characteristics
- Hemochromatosis is primarily caused by homozygosity for the p.Cys282Tyr variant in HFE in individuals of European origin 1.
- The disease leads to increased intestinal iron absorption and iron release from macrophages, resulting in an expanded circulating iron pool, reflected by increased transferrin saturation 1.
- Transferrin saturation can also be increased in patients with advanced cirrhosis, low transferrin, acute liver failure, and acute liver injury, which may be confused with a predisposition to hemochromatosis 1.
Pathogenesis and Genetics
- Hepcidin plays a crucial role in the pathogenesis of hemochromatosis, but its measurement is not necessary for diagnosis, as persistently increased transferrin saturation is a sufficiently specific marker of hepcidin deficiency 1.
- In individuals of non-European origin, or in individuals of European origin who are not homozygous for the p.Cys282Tyr variant in HFE, hemochromatosis is caused by rarer variants in the HFE or non-HFE-haemochromatosis genes 1.
Importance of Diagnosis and Treatment
- Correct diagnosis, adequate treatment, and appropriate follow-up are essential in the care and prevention of complications in patients with hemochromatosis 1.
- Early diagnosis and treatment can prevent organ damage and allow for normal life expectancy, emphasizing the need for prompt recognition and management of the disease.
From the Research
Definition of Hemochromatosis
- Hemochromatosis is a genetic disorder characterized by excessive absorption and accumulation of iron in the body 2
- It is one of the most common inherited disorders, leading to damage to various organs such as the liver, heart, pancreas, and joints 2, 3
- Hereditary hemochromatosis (HH) is an autosomal recessive genetic disease, characterized by an excessively increased absorption of dietary iron 3
Causes and Mechanisms
- The excess iron deposition can cause damage to various organs, including the liver, heart, pancreas, and joints 2
- Genetic polymorphisms of the HFE gene affect the normal activity of another protein, hepcidin, a negative regulator of iron homeostasis 3
- The lack of an effective excretory mechanism leads to toxic effects of excess iron 3
Clinical Manifestations
- If left untreated, hemochromatosis can lead to serious complications such as cirrhosis, diabetes, heart failure, and increased risk of certain cancers 2
- Iron overload in hemochromatosis significantly affects the cardiovascular system, leading to morbidity and mortality 2
- Clinical onset hereditary hemochromatosis symptoms occur more frequently in adult men than women, as the monthly loss of iron due to menstruation in women slows down accumulation and the symptoms usually start appearing after menopause 3
Treatment Options
- Therapeutic phlebotomy is the primary form of treatment for this disease so far, combined with the use of chelating agents 3
- Deferasirox, an oral iron chelator, has been shown to be effective in reducing iron burden in patients with hereditary hemochromatosis 4, 5, 6
- Orthotopic liver transplantation (OTL) is performed in patients with advanced cirrhosis 3