9760. Genetics. Hemochromatosis type I (gene HFE)

Genetic testing for HFE gene mutations associated with the development of type 1 hemochromatosis — an inherited disease in which excess iron accumulates in the body, damaging the liver, heart, pancreas, and other organs.

Type 1 hemochromatosis is the most common form of inherited iron metabolism disorder, in which excess iron accumulates in organs and tissues, eventually leading to their damage.

The cause of the disease is mutations in the HFE gene, in particular:

• C282Y (rs1800562) – the most significant, with high penetrance;
• H63D (rs1799945) – less aggressive, but when combined with C282Y, increases the risk;
• S65C (rs1800730) – rare, with low clinical significance, but taken into account in combined genotypes.

In patients with a homozygous or combined mutation, the following may be observed:

• increased ferritin levels and transferrin saturation with iron;
• persistent fatigue, weakness, decreased libido, skin pigmentation, arthralgia;
• progression to liver cirrhosis, diabetes mellitus, cardiomyopathy, hypogonadism.

The disease responds well to treatment with phlebotomy (bloodletting), therefore early detection is of great importance.

Genotypes:

• Normal: C/C (H63D), A/A (S65C), G/G (C282Y)
• Heterozygous: carrier status (risk of developing or transmitting the disease)
• Homozygous: highest risk of developing hemochromatosis

Important:

• The disease has an autosomal recessive inheritance pattern, meaning that it manifests when two defective alleles are present.
• It is more often diagnosed in men after the age of 30-40; women have protection in the form of regular blood loss (menstruation).
• Successful treatment is possible provided the disease is detected early, therefore genetic testing is especially recommended in cases of unexplained elevated ferritin levels.

• Individuals with elevated ferritin levels, transferrin saturation, or blood iron levels.
• Patients with liver damage of unknown etiology, diabetes mellitus, cardiomyopathy, or hypogonadism.
• People with a family history of hemochromatosis.
• In cases of decreased libido, chronic fatigue, or skin pigmentation of unknown origin.
• Before long-term use of iron-containing medications.

• Venous blood

In order to exclude factors that may affect the test results, we recommend to follow the preparation rules: