Primary hemochromatosis: causes, symptoms, diagnosis, treatment

Primary hemochromatosis is a congenital disease, characterized by a marked accumulation of iron, causing tissue damage. The disease is not clinically manifested until the development of organ damage, often irreversible. Symptoms of the disease include weakness, hepatomegaly, bronze skin pigmentation, loss of libido, arthralgia, manifestation of cirrhosis, diabetes, cardiomyopathy. The diagnosis is based on the definition of serum iron and genetic studies. Treatment is a series of phlebotomies.

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Epidemiology

The disease is autosomal recessive, the frequency in Northern Europe of the homozygous form is 1: 200, and the heterozygous form is 1: 8. The disease is rare in Asia and Africa. Patients with clinical hemochromatosis in 83% of cases are homozygotes.

The disease, as a rule, does not manifest until middle age. In 80-90% of people at the time of the development of symptoms the total iron reserves are greater than the South.

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Causes of the primary hemochromatosis

Almost all primary hemochromatosis is caused by a mutation of the HFE gene . Primary hemochromatosis, not associated with HFE, is rare and includes ferroporinic disease, juvenile hemochromatosis and very rare neonatal hemochromatosis, hypotransferrinemia and acetuloplasminemia. The clinical consequences of iron overload are the same for all types of diseases.

More than 80% of HFE-mediated hemochromatosis is caused by a homozygous mutation of C282Y or a combined heterozygous mutation C282Y / H63D. The mechanism of iron overload is the increased absorption of it from the digestive tract. Hepsidine, a newly identified peptide synthesized by the liver, controls the mechanism of iron absorption. Hepsidine with the normal HFE gene prevents excess absorption and iron accumulation in healthy people.

The total iron content in the organism in this pathology can reach 50 g in comparison with the normal level of about 2.5 g in women and 3.5 g in men. The deposition of iron in the organs catalyzes the generation of free reactive hydroxyl radicals.

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Symptoms of the primary hemochromatosis

Since iron accumulates in many organs and tissues, the symptoms can be multi-organ or systemic. In women, weakness and systemic symptoms develop early; in men, cirrhosis or diabetes are frequent initial manifestations of hemochromatosis. Hypogonadism is typical for patients of both sexes and can cause various manifestations. Liver disease is the most frequent complication and usually progresses to cirrhosis, and in 20-30% of cases it is transformed into hepatocellular carcinoma. In 10-15% of untreated patients, heart failure develops, 90% have severe skin pigmentation, 65% have diabetes and its potential complications (nephropathy, retinopathy, neuropathy) and 25-50% have arthropathy.

Juvenile hemochromatosis

A rare autosomal recessive disease caused by a mutation of the HJV gene, which disrupts the transcription of the hemeiculin protein. It is mainly found in adolescents. The ferritin level is more than 1000, transferrin saturation is more than 90%. Symptoms and signs include progressive hepatomegaly and hypogonadotropic hypogonadism.

Diagnostics of the primary hemochromatosis

Suspicion of hemochromatosis occurs in the presence of typical symptoms, especially with unexplained violations of the liver function, as well as in patients who have a family history. Since the symptoms develop only after tissue damage, the diagnosis is desirable prior to the development of symptoms (which is often difficult). If suspicion of hemochromatosis is determined by serum iron, saturation of serum transferrin, serum ferritin, gene studies are performed.

Serum iron is elevated (> 300 mg / dL). The saturation of serum transferrin is usually more than 50% and often more than 90%. The level of serum ferritin is increased. Genetic research is the determining method of diagnosis. It is necessary to exclude other mechanisms of iron overload, such as congenital hemolysis (for example, in sickle-cell anemia, thalassemia). The iron content in the liver can be determined using a high-intensity MRI. Since the development of cirrhosis worsens the prognosis, it is recommended to perform a liver biopsy with an inexplicably high level of serum ferritin (eg,> 1000), while taking into account the age at which ferritin levels may increase and the increased activity of liver enzymes that can lower the ferritin level . Determination of the iron content in the liver can confirm the deposition of iron in the tissues. Relatives of the first line of patients with primary hemochromatosis should be examined. In more than 95% of cases, C282Y and H63D are determined.

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Treatment of the primary hemochromatosis

Phlebotomy is a simple method of removing excess iron in most cases, which prolongs survival, but does not prevent the development of hepatocellular carcinoma. After the diagnosis, about 500 ml of blood (about 250 mg of iron) is exfused weekly until the serum iron level is normalized and the transferrin saturation is less than 50%. Weekly phlebotomy may be needed for several years. When the level of iron is normalized, further phlebotomies are performed to maintain a saturation level of transferrin less than 30%. Treatment of diabetes, cardiac disorders, erections and other secondary manifestations is carried out in the presence of indications.