Causes of hemochromatosis. Hemochromatosis is a genetic liver disease with serious complications, treatment and prognosis

Hemochromatosis is a hereditary disease characterized by a violation of iron metabolism, resulting in an excessive accumulation of this element in the tissues of the body (more than 20 g at a rate of 3-4 g). The name of the nosological form reflects the most characteristic symptom for this disease - intense staining. skin and internal organs.

A symptom complex typical of hemochromatosis was first described in the second half of the 19th century.

According to statistics, the probability of hemochromatosis in the population is 0.33%.

Synonyms: pigmentary cirrhosis, bronze diabetes.

Excessive accumulation of iron in liver tissues

Causes and risk factors

The cause of hereditary hemochromatosis is a genetically determined predisposition associated with a mutation of the genes responsible for the main stages of the metabolism of iron-containing pigments in the body (C282Y and H63D).

Secondary hemochromatosis is formed against the background of the acquired insolvency of the enzyme systems involved in the exchange of iron in the body. The main pathologies leading to the development of secondary hemochromatosis:

• chronic viral hepatitis C and B;
• non-alcoholic steatohepatitis;
• liver tumors;
• leukemia;
• blockage of the pancreatic ducts;
• cirrhosis of the liver;
• thalassemia.

The accumulation of iron in tissues and organs can cause the development life threatening conditions - hepatic or diabetic coma, hepatic and heart failure, bleeding from dilated superficial veins.

Forms of the disease

The main forms of hemochromatosis are primary and secondary, and the primary is not a monogenic disease. Depending on the type of mutation, the following variants of primary (hereditary) hemochromatosis are distinguished:

• autosomal recessive;
• juvenile;
• autosomal dominant;
• associated with a mutation of the type 2 receptor for transferrin.

Stages of the disease

Hemochromatosis has the following stages:

1. Without overloading the body with iron.
2. With iron overload without clinical symptoms.
3. With severe clinical manifestations of pathology.

Symptoms

The early stages of the pathological process are characterized by the presence of such general clinical symptoms of intoxication:

• increased fatigue, progressive weakness;
• loss of appetite;
• weight loss;
• unmotivated weakening of sexual function.

A symptom complex typical of hemochromatosis was first described in the second half of the 19th century.

Excessive accumulation of iron in tissues and organs leads to pain in the joints and right hypochondrium, skin atrophy, testicular atrophy in men.

The classic triad of symptoms of hemochromatosis:

• bronze pigmentation of the skin and mucous membranes;
• diabetes;
• cirrhosis of the liver.

Features of the course of the disease in young people

In young people from 15 to 30 years old, the so-called juvenile form of hemochromatosis is formed, which is characterized by a pronounced overload of the body with iron with a violation of the functional activity of the liver and heart.

Diagnostics

Diagnostic clinical criteria for hemochromatosis:

• diabetes;
• hypogonadism;
• cardiomyopathy;
• skin pigmentation.

The laboratory criterion is a transferrin saturation ratio of 45% or more.

The most informative non-invasive diagnostic method is magnetic resonance imaging of the liver, which makes it possible to note a decrease in the signal level due to excessive accumulation of iron in its cellular structures.

According to statistics, the probability of hemochromatosis in the population is 0.33%.

Treatment

The main pathogenetic method of treating hemochromatosis is bloodletting, as a result of which an excess amount of iron is eliminated from the body. Pharmacological methods of removing iron based on the intake of iron-binding drugs are also used.

Symptomatic treatment consists of measures aimed at eliminating the manifestations diabetes maintaining the functional activity of the liver and heart.

Possible complications and consequences

In addition to the pronounced toxic effects of excessive iron concentration on the body, its accumulation in tissues and organs can cause the development of life-threatening conditions - hepatic or diabetic coma, liver and heart failure, bleeding from dilated superficial veins.

Forecast

Hemochromatosis is a serious disease, the prognosis of which depends on the degree of iron accumulation in the body and on the compensatory capabilities of the organs and systems involved in the pathological process. Timely started and regularly carried out pathogenetic therapy can increase life expectancy by several decades.

Prevention

Since primary hemochromatosis is hereditary, there are no measures to prevent it. To the number preventive measures secondary hemochromatosis include:

• following a diet that limits the intake of foods rich in iron;
• taking iron-binding drugs.

Video from YouTube on the topic of the article:

Patients have an A77D mutation (conversion of alanine to aspartic acid) in the SLC40A1 gene (locus 2q32), encoding the synthesis of the transport protein ferroportin. Age of onset is over 60 for men and 70 for women. Distinctive clinical features are: early accumulation of iron in reticuloendothelial cells and a significant increase in serum ferritin levels even before an increase in the transferrin saturation coefficient with iron.

• Epidemiology of hemochromatosis

  The incidence among residents of the European community with hemochromatosis ranges from 1:300 to 1:10-12 people.

  The incidence of hemochromatosis among blacks is lower than among people of other ethnic groups (0.14:1000 population); at the same time, for example, among the Spaniards, these values ​​are higher: 0.27:1000 population.

  Hereditary hemochromatosis occurs with a frequency of 1.5-3:1000 of the population. The most common form of hereditary hemochromatosis (more than 95% of all cases) is mediated by two mutations in the HFE gene located on chromosome 6 (type I hemochromatosis): C282Y and H63D.

  In the US, the incidence of primary hemochromatosis is 1:200-500 of the population. In 5.4% of cases, the C282Y mutation in the HFE gene is detected; 13.5% - mutation H63D. Homozygotes for the C282Y mutation are 0.25% of the population; homozygotes for the H63D mutation - 1.89%.

  In the world homozygotes for mutations C282Y and H63D are 1.9 and 8.1% of the population, respectively. Type I hemochromatosis is common in northern Europeans. Thus, approximately 93% of the Irish population are homozygous for the C282Y mutation.

  Over the past 20 years, a high prevalence of hereditary hemochromatosis has been revealed in people with human leukocyte antigen HLA-A3, -B7, -B14, -A11 (72-78% HLA-A3 and 20-22% HLA-B14).

  Men (mainly aged 40-60 years) get sick more often than women (1.8-3:1). In the US, the incidence of the disease is 0.034% in women and 0.68% in men.

  Men are more likely than women to have such serious complications of hereditary hemochromatosis as: diabetes mellitus (15.9 and 7.4%, respectively), cirrhosis of the liver (25.6 and 13.8%, respectively). Women are more likely than men to experience fatigue (64.8 and 425, respectively) and skin hyperpigmentation (48 and 44.9%, respectively).

  Clinical symptoms hemochromatosis develops in men over the age of 40 ( average age the onset of the disease - 51 years); in women - after 50 years (the average age of onset of the disease is 66 years).

  Mortality from hemochromatosis is 1.7:10 thousand deaths. According to the autopsy results, this figure is higher: 3:210 thousand deaths.

  Mortality rates from hemochromatosis are higher in children and in patients over the age of 50 years (5.6: 1 million population). The main causes of death are: cirrhosis, liver cancer, heart failure.

• iron metabolism

  The important role of iron for the human body was established as early as the 18th century. Iron is indispensable in the processes of hematopoiesis and intracellular metabolism. This element is part of the blood hemoglobinresponsible for the transport of oxygen and the performance of oxidative reactions. Iron, being an integral part of myoglobin and hemoglobin, is part of cytochromes and enzymes involved in redox reactions. Read more: Iron.

  Normal body stores of iron are 300–1000 mg for adult women and 500–1500 mg for adult men.

  The daily iron requirement is 10 mg for men and 20 mg for women. It is believed that the optimal intensity of iron intake is 10-20 mg / day. Iron deficiency can develop if the intake of this element in the body is less than 1 mg / day.

  The amount of iron in the body varies with weight, hemoglobin concentration, gender, and depot size. The largest depot is hemoglobin, in particular in circulating red blood cells. Iron reserves here vary according to body weight, gender and blood hemoglobin concentration and account for approximately 57% of all iron contained in the human body. For example, a person weighing 50 kg whose blood hemoglobin concentration is 120 g/l has a heme iron content of 1.1 g. , from its loss (from bleeding), pregnancy or iron overload (with hemochromatosis). The tissue pool of iron includes myoglobin and a tiny but essential fraction of iron in enzymes. Approximately 9% of iron is found in myoglobin. There is a "labile pool" - a fast recirculation component that does not have a specific anatomical or cellular location.

  Adequate nutrition and therapy should not only correct the iron deficiency, but also replenish lost iron stores. Safe intake of iron in dietary nutrition is up to 45 mg / day.

  Daily loss of iron is approximately 1 mg per day. They are mainly carried out through the digestive tract: desquamation epithelial cells intestines (0.3 mg / day), microbleeding and loss with bile. Iron is also lost during desquamation of skin epithelial cells and to a lesser extent in the urine (less than 0.1 mg/day).

  In healthy people, these losses are compensated by the absorption of iron from food. The normal balance of iron is maintained to a large extent by the regulation of its absorption. The received inorganic iron is solubilized and ionized by acidic gastric juice, and is also reduced to the glandular and chelate forms. Substances that form low molecular weight chelated iron (such as ascorbic acid, sugar, and amino acids) promote iron absorption. Normal gastric secretion contains a stabilization factor and a likely endogenous complex that helps slow the deposition of dietary iron at an alkaline pH. small intestine.

  The ferrous form of iron is more soluble than the trivalent form. Thus, ferrous iron more easily crosses the mucosal layer in order to reach the brush border of the small intestine. There it is oxidized to ferric iron before entering the enterocyte.

  In the epithelial cell membrane, iron binds to a receptor protein that transports it into the cell. Apotransferrin in the cytosol of intestinal epithelial cells can accelerate the absorption of iron. The rate increases with iron deficiency, and this probably plays a regulatory role, facilitating iron absorption when the need for iron increases.

  Most of the iron that is absorbed from the intestinal lumen quickly passes through the epithelial cells in the form of small molecules. Plasma iron is oxidized by ceruloplasmin, which functions as a ferroxidase, and then taken up by transferrin. This route usually takes 20-30 mg of iron per day. The portion of cytosolic iron that exceeds the fast transport capacity combines with apoferritin to form ferritin. Some of the iron from ferritin may later be released into circulation, but more remains in the mucosal cells until they are shed into the intestinal lumen. Direct supply of iron to lymphatic vessels slightly. Ferritin is synthesized by many types of cells, but mainly by the cells of the liver and spleen, which are the main depots of iron in the body. The rate of ferritin synthesis is regulated by the intracellular iron content, and part of the formed ferritin enters the circulation through active secretion or reverse endocytosis, and the amount of ferritin circulating in the blood corresponds to iron stores.

  Thus, iron is transported and deposited by transferrin, the transferrin receptor, and ferritin.

  Extracellular iron compounds also include lactoferrin, which is similar in structure to transferrin, and heme-binding protein, hemopexin.

  The main regulator of iron balance is the level of iron absorption in the gastrointestinal tract. With a deficiency of iron in the body, the absorption process increases, and with an excess it decreases. Iron absorption occurs in the small intestine and is especially intense in the enterocytes of the duodenum.

  The process of iron absorption begins with the migration of pluripotent progenitor cells located inside the intestinal crypts to the villi. At the final stage, progenitor cells turn into mature erythrocytes capable of transporting iron.

  Metabolism of iron in the body healthy person.

  Only 1 mg/day of iron is absorbed in the gastrointestinal tract. Therefore, the main need for iron is satisfied by its reutilization from decaying erythrocytes, maintaining a constant balance of iron in the body, and the reutilization processes proceed quite intensively.

  After absorption from the gastrointestinal tract, iron is transported into the plasma primarily in the form of iron bound to transferrin. Subsequently, the iron-transferrin complex interacts with transferrin receptor 1 (RTf1), which is present in various organs, in particular the liver and erythropoietic cells.

  The half-life of the iron-transferrin complex does not exceed 60-90 minutes. With enhanced erythropoiesis, the half-life of the complex is reduced to 10-15 minutes. Under normal conditions, most of the iron (coming from the intestine (5%) and from the recycling of old erythrocytes of the mononuclear macrophage system (95%)), transported by troansferrin, is transferred to the bone marrow, where it participates in the synthesis of hemoglobin.

  AT bone marrow the iron-transferrin complex penetrates into the cytoplasm of erythrocyte precursors, in which iron is released from the complex and incorporated into the heme porphyrin ring. Heme is incorporated into hemoglobin and, as part of a new red blood cell, iron leaves the bone marrow.

  The process of transporting iron by transferrin to the bone marrow is carried out 10-20 times a day. Every day in the body of an adult, 0.8% of circulating red blood cells are renewed. Each 1 ml of blood contains 1 mg of elemental iron. Iron not utilized by erythrocyte precursors is stored in the spleen, liver, and bone marrow in the form of ferritin.

  With an excess of dietary or drug iron, despite a decrease in its absorption in percentage terms, iron overload develops, the consequences of which are clinically manifested in hemolytic conditions, frequent blood transfusions and in patients with hemochromatosis.

The dominance of one of them (usually cirrhosis of the liver) is characteristic of the early stage of the disease, the developed symptoms are usually observed in the terminal stage.

As the disease progresses, the following clinical syndromes:

• Complications of hemochromatosis

  With the progression of the disease, after the formation of liver cirrhosis in a patient, the course of hemochromatosis may be complicated by the occurrence of liver failure.

  Almost 30% of patients with hemochromatosis develop liver cancer. The frequency of this complication increases with age. Hepatocellular carcinoma is a common cause of death in hemochromatosis. And the risk of its occurrence in patients with hemochromatosis is 200 times higher than the average in the population. Liver cancer is found in patients with already developed cirrhosis of the liver. However, the likelihood of its occurrence of cancer does not correlate with either the degree of liver damage or the effectiveness of the treatment.

  Complications of hemochromatosis also include: arrhythmias, myocardial infarction, congestive heart failure, bleeding from dilated veins of the esophagus, diabetic and hepatic coma (rarely observed).

  Patients with hemochromatosis are prone to various infections (including the development of sepsis), which can be caused by microorganisms that rarely affect healthy people (for example, Yersenia enterocolitica and Vibrio vulnificus).

The liver in patients with hemochromatosis is enlarged, dense, smooth and often painful. The liver can be enlarged in the absence of complaints or with unchanged liver function tests.

In the final stage of the disease, macronodular cirrhosis of the liver develops; 30-50% of patients have splenomegaly.

• Symptoms of Hemochromatosis Most Commonly Found on Physical Examination

  Symptoms	Frequency (%)
  Hepatomegaly	60-85
  Cirrhosis of the liver	50-95
  Skin pigmentation	40-80
  Arthritis	40-60
  Diabetes	10-60
  Splenomegaly	10-40
  Hair loss	10-30
  testicular atrophy	10-30
  Dilated cardiomyopathy	0-30

Decreased ferritin reflects iron deficiency in iron deficiency anemia.

• Determination of the content of transferrin in blood serum.

  A decrease in transferrin content may indicate not only hemochromatosis, but also any disorder associated with inflammation or necrosis. chronic inflammation or a malignant tumor, especially the lower intestines; about nephrotic syndrome; hereditary atransferrinemia; multiple myeloma.

  An increase in transferrin may indicate an increased level of estrogens in the body (for example, during pregnancy, taking oral contraceptives) or an iron deficiency (increased levels of transferrin often precede the onset of anemia).

• Determination of the total iron-binding capacity of serum.

  Normally, the total iron-binding capacity of serum is 2.50-4.25 mg/l or 44.8-76.1 µmol/l. With hemochromatosis, this figure decreases.

• Determination of the calculated coefficient of saturation of transferrin with iron (ITI).

  The transferrin iron saturation coefficient is a calculated value [ITI = (serum iron / total serum iron-binding capacity x100%]. TIT accurately reflects iron stores in the body. However, an increase in TIT can indicate not only hemochromatosis, but also excessive iron intake, thalassemia, deficiency vitamin B 6, aplastic anemia; its decrease in hypochromic anemia, malignant tumors of the stomach and small intestine.

  An important laboratory sign of hemochromatosis is an increase in the coefficient of NTJ: in men it is above 60%, in women it is above 50%. With hemochromatosis, this figure can reach 90% (normally 25-35%). The sensitivity of the method is 90%; specificity - 62%.

• Desferal test.

  This study allows you to confirm the presence of iron overload. After intramuscular injection of 0.5 g of deferoxamine (Desferal), the daily excretion of iron in the urine significantly exceeds normal level(0-5 mmol / day), amounting to 3-8 mg or more.

  A test with desferal, reflecting the reserves of easily mobilized iron, can give false negative results, for example, with a deficiency of ascorbic acid. In patients with hemochromatosis, ascorbic acid enhances the absorption and increases the toxicity of iron, so its deficiency can lead to depletion of the depot of easily mobilized iron, which is detected by the desferal test.

• Carrying out molecular genetic analysis

  Molecular genetic diagnosis of hemochromatosis is based on the identification of two common mutations in the HFE gene - C282Y and H63D, associated with an increased risk of the disease. Diagnosis is carried out within 2-4 weeks. Allows you to confirm the hereditary nature of hemochromatosis and exclude the secondary nature of iron overload.

  The diagnosis of hereditary hemochromatosis is established in the presence of homozygous mutations in the HFE gene (C282Y or H63D) or in the detection of complex heterozygotes (a combination of heterozygous mutations in C282Y and H63D) in patients with laboratory signs of iron overload. Isolated heterozygous mutations C282Y and H63D occur in the population of healthy people with a frequency of 10.6% and 23.4% of cases, respectively; the presence of these mutations is not a basis for the diagnosis of hereditary hemochromatosis.

  Molecular genetic diagnosis of hemochromatosis is carried out in patients with clinical symptoms of hemochromatosis and/or typical deviations of iron metabolism to confirm/clarify the diagnosis, as well as in relatives of such patients in order to diagnose their disease at the preclinical stage and timely start its treatment.

  More than 90% of homozygotes with the C282Y mutation develop severe iron overload, which corresponds to an iron content in the liver tissue of more than 4500 μg (or 80 mmol) per 1 g of dry weight in an adult patient. This overload is present in less than 5% of complex heterozygotes.

• • X-ray examinations of the joints.

    An x-ray examination of the joints reveals signs of hypertrophic osteoarthritis (cystic changes in sclerotic subchondral bone surfaces, loss of articular cartilage with narrowing of the joint spaces, diffuse demineralization, hypertrophic bone proliferation and calcification of the synovial membranes), chondrocalcinosis of the menisci and articular cartilage.

  • CT scan of the abdominal organs.

    During the study, it is possible to detect an increased density of liver tissue due to iron deposits or to suspect the presence of hemochromatosis. However, if the level serum iron exceeds the norm by less than 5 times, then using this method it is impossible to detect signs of iron overload. Liver CT is also performed to exclude the diagnosis of hepatocellular carcinoma.

  • MRI of the abdominal organs.

    The liver of a patient with hemochromatosis in the pictures has a dark gray or black color. MRI is informative in the diagnosis of hemochromatosis with a significant overload of internal organs with iron. However, this study cannot eliminate the need to perform a liver biopsy with subsequent histological examination of the obtained tissue samples. MRI of the liver is also performed to exclude the diagnosis of hepatocellular carcinoma.

    
    On an MRI image of a patient with hemochromatosis, the liver is visualized as an area of ​​reduced density in black.
  • Evaluation of the results of a liver biopsy.

• Survey Tactics

  Diagnosis of hemochromatosis is based on the determination of indicators of iron metabolism, since biochemical liver tests for a long time, even at the stage of liver cirrhosis, remain normal and do not correlate with the level of accumulation of iron in the liver.

  The following changes in laboratory parameters are considered pathognomonic for hemochromatosis:

  • An increase in the content of iron in the blood serum up to 54-72 µmol / l.
  • An increase in the content of ferritin - more than 900mkg / l.
  • Decreased total iron-binding capacity of serum less than 40 µmol/L.
  • Decrease in serum transferrin content less than 2.6 g/l.
  • An increase in transferrin iron saturation ratio of more than 60% (is a non-invasive informative screening test for the presence of iron overload).

  If the saturation ratio of transferrin with iron is greater than 45%, then the next step in the diagnosis should be genetic testing of the patient for the presence of C282Y and/or H63D mutations.

  If the patient is a homozygous carrier of C282Y, H63D mutations or a complex heterozygous carrier of C282Y/H63D mutations, then the diagnosis of hereditary hemochromatosis is considered established. To verify the diagnosis in these cases, a liver biopsy is not required.

  If the patient's liver enzymes are within the normal range, the ferritin content is less than 1000 μg / l and the patient's age is less than 50 years, then a liver biopsy should be performed to determine the liver iron index, which is calculated as the ratio of the iron content in the liver tissue (in μmol / g dry weight) to the age of the patient (in years). If the hepatic iron index exceeds 1.9, then the diagnosis of hereditary hemochromatosis can be considered established.

• Differential diagnosis of hemochromatosis

  The differential diagnosis of hemochromatosis should be made with the following diseases:

  Disease	Overload mechanism
  Thalassemia, sideroblastic anemia, congenital dyserythropoietic anemia	Ineffective erythropoiesis + blood transfusion
  Blood transfusion, iron supplementation, Bounty syndrome	Excess iron intake + genetic factor
  Atransferrinemia, ceruloplasmin deficiency	Defects in iron transport and metabolism
  tardive cutaneous porphyria
  Hereditary hemolytic anemia	Inherited linked to the HFE gene
  Alcoholism, non-alcoholic steatohepatitis, portocaval shunt	Increased absorption of dietary iron
  Local siderosis (pulmonary, hepatic)	RBC diapedesis, chronic intravascular hemolysis

Hemochromatosis, or bronze diabetes, is a hereditary polysystemic pathology associated with impaired absorption of iron. As a result, iron is actively absorbed in the digestive tract and accumulates in the liver, heart muscle, and pancreas. The liver suffers the most from iron overload.

Liver hemochromatosis - common genetic disease, develops mainly in men. Women get sick 3 times less often. The first symptoms of bronze diabetes in 70% of patients appear after 40 years. Pathology leads to serious dysfunctions in the body and, if left untreated, leads to the development of liver cancer and other serious conditions.

The reasons

Based pathogenetic mechanisms the formation of the disease distinguish primary hemochromatosis (hereditary) and secondary. The hereditary form of pathology is associated with a gene defect. The HFE gene responsible for the development of bronze diabetes is located on chromosome 4, on the left shoulder. Pathology often develops in individuals who have received 2 copies of the defective gene - simultaneously from the father and mother.

The secondary form develops for a number of reasons:

• Thalassemia is a hereditary hemoglobinopathy in which the protein molecules that make up the structure of hemoglobin are destroyed. Individuals with thalassemia are prone to developing hemolytic crises due to excess iron.
• Diseases affecting the liver. Hepatitis, alcoholic cirrhosis, chronic hepatic porphyria, malignant tumors increase the likelihood of developing a secondary form.
• Blood transfusion. The blood from a donor contains foreign red blood cells that die before their own red blood cells. When they break down, they secrete iron, the excess of which accumulates in the internal organs.
• Excessive intake of iron into the body from the outside due to uncontrolled long-term use of iron-containing drugs.

Occasionally, the secondary form occurs in individuals on a long-term low-protein diet and in patients requiring continuous hemodialysis.

Symptoms

In the initial stages, hemochromatosis does not give a bright clinical picture. Occasionally, patients may complain of mild malaise and fatigue. Alarming signs appear as the total concentration of iron in the body increases. When this indicator becomes critical (up to 40 g), the clinical picture becomes significant. Depending on the prevailing symptoms, bronze diabetes can proceed according to the hepatopathic, cardiopathic, endocrinological type.

The hepatopathic type of pathology develops frequently (up to 70% of the total number of patients). Excess iron accumulates in the liver, leading to disruption of its functioning. As a result, a symptom complex develops:

• Pain in the abdominal region of a diffuse nature. Pain disturbs 40% of patients and is combined with dyspepsia.
• Dyspeptic manifestations. Patients are concerned about episodic nausea, vomiting. Often diarrhea develops in the form of watery stools, the frequency of which reaches up to 20 times a day.
• Enlargement of the liver with subsequent development of fibrosis and cirrhosis.
• Dryness of the skin.

The cardiopathic form (myocarditis pigmentosa) develops when excess iron accumulates in the myocardium and blood serum. Pigmentary myocarditis is detected in 20% of the total number of patients. The disease proceeds with signs of cardiovascular disorders:

• Failures of the heart rhythm in the form of attacks of tachycardia, atrial fibrillation.
• Enlargement of the heart in size, expansion of its cavities.
• Decreased blood pressure.
• The appearance of peripheral edema.

The course of hemochromatosis according to the endocrinological type occurs against the background of damage to the pituitary gland and pancreas. As a result, there is a violation of the synthesis of hormones, sexual dysfunction and insulin-dependent diabetes mellitus develop. 40% of men have impotence; 15% of women have secondary amenorrhea and inability to conceive.

Other specific manifestations include:

• The appearance of atypical pigmentation of the skin, which is due to the accumulation of excess iron in the skin and the deposition of hemosiderin - a special pigment dark yellow formed from the breakdown of hemoglobin. Pigmentation of the skin appears on the face, hands, external genitalia, in the armpits. The skin takes on a bronze color.
• Arthralgia. In 40% of patients, pain occurs in the interphalangeal, ulnar, knee joints. Sometimes joint deformity is added to pain and limited mobility.
• Change appearance. Patients with hemochromatosis are characterized by the absence of hair on the head and body, deformation of the nail plates.

The terminal stage is difficult. The concentration of iron in the body reaches critical levels, exceeding the natural norm by 5 times or more. Patients in the final stages of the disease suffer from portal hypertension, ascites, and progressive wasting (cachexia).

Hemochromatosis in children can give a clinical picture from the first months of life, if the cause of the disease is heredity. Overloading the child's body with iron for other reasons is extremely rare. Illness in childhood appears as:

• Increased excitability.
• Protracted neonatal jaundice in newborns.
• Excessive dry skin and hair loss.
• Low physical activity.
• Negative weight dynamics.

The appearance of dark pigmentation on the skin occurs gradually. In almost all children with hemochromatosis, the skin is thin and easily vulnerable. Closer to preschool and primary school age, such children experience persistent disorders in the functioning of the heart, liver, and spleen.

Complications

If untreated, hemochromatosis leads to the development of life-threatening complications. Due to the high concentration of iron in the body - especially in the liver - the risk of developing liver failure increases, when the iron completely loses all functions. Against the background of the failure of the liver, the brain is affected by intestinal toxins and the patient falls into a coma.

A serious complication of hemochromatosis with a high mortality rate is myocardial infarction and acute heart failure. With a long course of pathology, internal hemorrhage arising from the dilated veins of the esophagus leads to death. A critical increase in the concentration of sugar in the blood causes a diabetic coma, often ending in death.

Diagnostics

When examining patients with suspected hemochromatosis, consultations of several specialists will be required - a gastroenterologist, a cardiologist, a surgeon, an endocrinologist, a dermatologist. During the initial examination, the doctor pays attention to the specific color of the skin (hemosiderosis), the absence of hairline and spoon-shaped nails. During palpation, an enlarged liver and spleen are determined. In the presence of cirrhosis, the liver feels hard, with a bumpy surface.

Laboratory diagnosis is an important point in confirming the diagnosis. General analysis blood is not informative, it is carried out only to exclude anemia. Valuable information is provided by a blood test for biochemistry. In patients, changes in biochemical parameters are revealed:

• An increase in bilirubin over 25 mmol / l.
• Increased ALAT, ASAT and GGT.
• An increase in blood glucose concentration over 5.8.

It is mandatory to conduct a dynamic blood test to determine the metabolism of iron. Diagnostics is carried out in stages:

• Stage 1 - detect the concentration of siderophilin (iron carrier protein in blood plasma); if the norm is exceeded (16–44 mmol / l), they proceed to the next stage.
• stage 2 - carry out a test for the concentration of ferritin; if the indicator exceeds 200 for women under 45–50 years old and 300 for men (women over 45–50 years old), they proceed to the final stage.
• Stage 3 - conducting an indirect quantitative phlebotomy, during which 200 mg of iron is extracted weekly from a patient with suspected hemochromatosis by bloodletting. If the patient's condition improves after the removal of iron in the amount of 3 g from the body, the diagnosis is considered confirmed.

Hereditary hemochromatosis is detected using genetic DNA analysis. The molecular genetic diagnostic method helps to identify the hereditary constitution of the organism and establish the predominant type of mutation in the genes. The advantages of the method are high information content and the possibility of confirming the diagnosis at the initial stages.

In the process of a comprehensive examination, it is important to determine the degree of damage to internal organs. This requires a number of high-precision studies:

• X-ray of the joints.
• ECG and echocardiography.
• Echography of the abdominal organs.
• MRI of the liver.

A reliable method for determining the prognosis for the further course of the pathology is a liver biopsy. In the biopsy sample extracted by puncture, the concentration of iron is determined. The higher this indicator, the worse the prognosis for survival.

Treatment

Treatment of hemochromatosis is reduced to the removal of excess iron from the body and the fight against complications. At an early stage of treatment, vitamin therapy is organized - patients are prescribed a course of B vitamins, tocopherol, vitamin M (folic acid). Vitamin therapy is necessary to accelerate the process of removing excess iron.

Drug therapy includes the use of chelators - chemical substances leaving iron ions from the body. In practice, deferoxamine is often used in the form of intramuscular injections and intravenous infusions. With prolonged use of deferoxamine, the development of side effects- clouding of the lens.

Phlebotomy is an effective non-drug method to minimize high iron content in the body. The essence of the procedure is the systematic removal of a certain volume of blood (up to 500 ml weekly) from the body. Phlebotomy is carried out for a long time, for 2–3 years, until the concentration of iron in the blood reaches optimal levels.

Symptomatic therapy is reduced to the treatment of fibrosis and cirrhosis of the liver, cardiovascular and sexual disorders, diabetes. Patients with progressive arthropathy are shown the procedure for arthroplasty of destroyed joints. Liver transplantation can save lives in patients with advanced cirrhosis.

Diet for hemochromatosis, as an integral part complex therapy assigned to all patients for life. The purpose of dietary nutrition is to prevent an increase in the concentration of iron in the body and maintain an optimal metabolism. Nutrition recommendations:

• Exclusion from the diet of bakery products, alcohol, seafood, offal (liver, kidneys).
• Minimizing the consumption of meat and foods high in ascorbic acid.
• The systematic use (in reasonable quantities) of black tea and coffee as drinks that can slow down the absorption of iron.

Forecast and prevention

Hemochromatosis refers to pathologies with a constantly progressive course. But the possibilities modern medicine allow to extend the life of patients for several decades. With an uncomplicated course, up to 80% of patients live longer than 10 years. If the disease is not treated, the prognosis for survival worsens - from the moment the diagnosis is confirmed, life expectancy does not exceed 5 years. From a persistent metabolic disorder, complications incompatible with life develop - cirrhosis, liver cancer, and extensive heart attack.

Prevention of primary hemochromatosis includes family screening, early detection and treatment of the disease. If the family has cases of morbidity in direct relatives, screening should be carried out as early as possible, before the formation of severe complications.

Prevention of secondary hemochromatosis includes:

• Balanced diet.
• Refusal of alcohol and nicotine.
• Acceptance of iron-containing preparations only as prescribed by a doctor and in the indicated dosage.
• Timely treatment of pathologies of the liver and blood.

With active absorption of iron in the intestine, followed by accumulation of the substance in other organs, liver hemochromatosis develops. The disease belongs to hereditary polysystemic pathologies, but can be acquired against the background of other diseases. The clinic is pronounced, intense and is manifested by a bronze tint of mucous membranes and skin. Complications - cirrhosis, cardiomyopathy, diabetes mellitus, arthralgia, sexual dysfunction. To make a diagnosis, specific laboratory tests. Treatment is based on bloodletting, on the principles of diet therapy and symptomatic therapy. According to the indications, transplantation of the affected organ or arthroplasty is performed.

A malfunction in the exchange of iron in the blood can cause a liver disease called hemochromatosis.

What it is?

What is hemochromatosis? This is a severe pathology, which is also called bronze diabetes, pigmentary cirrhosis due to a specific clinical picture characterized by pigmentation of the skin and internal organs. The disease refers to a semi-systemic disease of a genetic type caused by a mutation in the HFE gene. The disease is more often associated with a transmissible mutation of the HFE gene on the 6th chromosome, so it is called hereditary hemochromatosis.

Idiopathic hemochromatosis is manifested by a violation of the process of iron metabolism against the background of a gene mutation, as a result of which the substance is absorbed into the intestines with its further accumulation in other organs (heart, pituitary gland, liver, joints, pancreas), in tissues. Against the background of the ongoing process, polyorganic insufficiency develops. The disease is always accompanied by cirrhosis, diabetes mellitus and pigmentation of the dermis.

Prevalence

Among genetic pathologies, hereditary hemochromatosis is one of the most common. The maximum number of cases was recorded in northern Europe. A specific mutated hemochromatic gene is responsible for the appearance of the disease, which is present in the DNA of 5% of people on Earth, but only 0.3% of the population develops the disease. The prevalence among men is 10 times higher than among women. In 70% of patients, the first symptoms appear in 40-60 years.

Forms and stages of hemochromatosis

According to etiological factors, there are:

• Primary hemochromatosis, that is, the hereditary type. The primary form is associated with a congenital malfunction of enzyme systems, which provokes the accumulation of iron on the internal organs, which causes a gene mutation on the 6th DNA chromosome. There are 4 subforms of a hereditary disease, which differ in severity and localization:

1. autosomal recessive, HFE-associated (develops in 95% of patients);
2. juvenile;
3. congenital HFE-unassociated;
4. autosomal dominant.

• Secondary ailment, that is, acquired generalized hemosiderosis. A disease occurs due to damage to another serious illness. Acquired enzyme deficiency, which accelerates the accumulation of iron, is:

1. post-transfusion;
2. alimentary;
3. metabolic;
4. neonatal;
5. mixed.

According to the nature of the process, there are 3 stages of congenital and secondary disease:

• I - light, without load, that is, iron metabolism is impaired, but its concentration does not exceed the norm;
• II - moderate, with overload, but asymptomatic;
• III - with intense symptoms: pigmentation, dysfunction of the heart, kidneys, liver, pancreas, etc.

Causes and pathogenesis

There are a number of reasons that provoke the development of hemochromatosis:

1. Poor heredity is the cause of the idiopathic form of hemochromatosis. An ailment develops due to the degeneration of a gene that corrects metabolic processes involving iron. A disease such as a mutation in the HFE gene is inherited.
2. Other pathologies, such as cirrhosis, hepatitis B and C that have not been treated for more than six months, malignant tumors in the liver tissues or the hematopoietic system.
3. Vascular operations associated with porto-caval shunting in the portal vein.
4. Accumulation of fat in the "filter" parenchyma, not associated with alcohol intoxication.
5. Blockage of the main pancreatic duct.
6. The introduction of specific intravenous drugs that provoke an increase in the concentration of iron.
7. Transfusion. Alien red blood cells are destroyed faster than their own. As a result of their death, iron is formed.
8. Permanent hemodialysis.
9. Diseases associated with an increase in hemoglobin. When it is destroyed, a large number of metabolites and iron are formed.

All points, except for the first, provoke the development of secondary pathology.

With a hemochromatic change, there is an excessive accumulation of iron in the tissues of the organs, which begins to gradually destroy them. An inflammatory process begins at the site of the lesion. Local immunity in order to suppress the focus activates the process of scarring with fibrin. As a result, fibrosis of the affected organ develops and its insufficiency. The first to suffer is the liver, which is subsequently affected by cirrhosis.

Symptoms and course

Primary hemochromatosis does not manifest itself in the initial stages. Perhaps the development of general weakness and malaise. As the disease progresses, symptoms of disruption of the work of other organs appear, expressed:

• pigmentation of the dermis in the front part, in front of the forearm, on top of the hand, near the navel, nipples and genitals, which is associated with the deposition of hemosiderin and a small amount of melanin;
• lack of hair on the front and torso;
• non-localized abdominal pain of varying strength;
• gastrointestinal disorders, including nausea with vomiting, diarrhea, lack of appetite;
• dizziness;
• limitation of the motor ability of the joints due to their damage and deformation.

The most common symptom complex with hemochromatic changes is the symptoms of cirrhosis of the parenchyma, diabetes mellitus against the background of strong pigmentation of the dermis. Symptoms appear when the iron level exceeds 20 g, which is 5 times higher than the physiological norm.

The course of the disease is characterized by constant progression. In the absence of therapy, symptoms of irreversible changes and severe complications that threaten death immediately appear.

Complications and consequences

As the disease progresses, the following complications develop:

1. Liver dysfunction when essential functions are not performed.
2. Any cardiac arrhythmias and congestive heart dysfunction.
3. Infectious complications of a different nature.
4. Myocardial infarction.
5. Bleeding from varicose veins, more often in the esophagus and gastrointestinal tract.
6. Diabetic and hepatic coma with progression of diabetes and cirrhosis, respectively.
7. The development of tumors, often in the liver tissues.
8. Diabetes mellitus, which develops in 75% of cases.
9. Hepatomegaly, when the liver is enlarged.
10. Splenomegaly is an enlargement of the spleen.
11. Diffuse progressive cirrhosis of the parenchyma.
12. Arthralgia, when the joints are very sore. Particularly affected are the interphalangeal joints on the second and third fingers.
13. Sexual disorders such as impotence (in men). In women, amenorrhea develops, as a result, a decrease in libido.
14. Damage to the pituitary gland and, associated with this, hormonal deficiency.

Diagnostics

Because hemochromatosis causes various diseases the clinical picture may vary. Therefore, different specialists are able to diagnose pathology, such as:

• gastroenterologist;
• cardiologist;
• endocrinologist;
• gynecologist;
• urologist;
• rheumatologist;
• dermatologist.

But all doctors will use the same approach in diagnosing pathological condition, regardless of the cause and clinical picture. After a visual examination and assessment of the patient's complaints, a complex of complex laboratory and instrumental studies is prescribed to clarify the diagnosis and determine the severity of damage to the body.

Diagnostics is aimed at identifying the disease itself by specific methods, since the standard list of tests is not informative. To date, a step-by-step scheme for diagnosing a pathological condition is proposed, including the following steps:

1. Determination of the level of transferrin - a specific protein involved in the transfer of iron throughout the body. The norm is no more than 44%.
2. ferritin calculation. The norm of a substance in women during the period outside and after menopause is 200 and 300 units, respectively.
3. Diagnostic bleeding. The essence of the method is the extraction of a small amount of blood with the calculation of iron in the serum. Usually the patient gets better when the level of iron in the general circulation falls by 3 grams.

Laboratory methods

The clinical tests required to diagnose the disease are based on determining the level of iron itself and the substances involved in its metabolism and transport throughout the body. Such laboratory methods diagnostics like:

• specific analysis for the concentration of iron, ferritin, transferrin;
• positive desferal test - urine tests with calculation of excreted iron;
• assessment of the fall in the total iron-binding properties of blood.

To confirm the diagnosis, a puncture or dermis is performed, followed by a study for the presence / absence of hemosiderin deposits. The hereditary form of the disease is determined on the basis of data obtained from a molecular genetic study.

To assess the severity of damage to other organs and determine the prognosis, the following are carried out:

• liver tests;
• analyzes of biological fluids for sugar and glycosylated hemoglobin.

Instrumental techniques

In addition to clinical studies of the patient's biological fluids, instrumental examination, which allows you to get a more accurate picture of the course, the prevalence of the pathological process, and determine the damage to the body. For this purpose:

• x-ray of the joints;
• Ultrasound of the peritoneum;
• ECG, echocardiography;
• MRI, .

Hemochromatosis

What is Hemochromatosis -

Primary hemochromatosis (PHC) is an autosomal recessive, HLA-associated disease caused by a genetic defect characterized by a metabolic disorder in which there is an increased absorption of iron in the gastrointestinal tract.

What provokes / Causes of Hemochromatosis:

The disease was first described by M. Troisier in 1871 as a symptom complex characterized by diabetes mellitus, skin pigmentation, cirrhosis of the liver associated with the accumulation of iron in the body. In 1889, Reclinghausen introduced the term "hemochromatosis", reflecting one of the features of the disease: an unusual color of the skin and internal organs. It was found that iron first accumulates in the parenchymal cells of the liver, and then can be deposited in other organs (pancreas, heart, joints, pituitary gland).

Prevalence. Population genetic studies have changed the idea of ​​PHC as a rare disease. The prevalence of the PHC gene is 0.03-0.07% - so, until recently, 3-8 cases per 100 thousand of the population were observed. Among the white population, the frequency of homozygosity is 0.3%, the frequency of heterozygous carriage is 8-10%. In connection with the improvement of diagnostics, an increase in the incidence is noted. The incidence rate among residents of the European community averages 1: 300. According to WHO, 10% of the population have a predisposition to hemochromatosis. Men get sick about 10 times more often than women.

Pathogenesis (what happens?) during Hemochromatosis:

Normally, the body contains about 4 g of iron, of which g is in the composition of hemoglobin, myoglobin, catalase and other respiratory pigments or enzymes. Iron reserves are 0.5 g, of which part is in the liver, but with histological examination they are not visible on iron by conventional methods. Normally, a person's daily diet contains about 10-20 mg of iron (90% in free standing, 10% in combination with heme), of which 1-1.5 mg is absorbed.

The amount of absorbed iron depends on its reserves in the body: the higher the need, the more iron is absorbed. Absorption occurs primarily in the upper small intestine and is an active process in which iron can be transported further against the concentration gradient. However, the mechanisms of transfer are unknown.

In the cells of the intestinal mucosa, iron is located in the cytosol. Some of it binds and is stored as ferritin, which is subsequently either used or lost as a result of desquamation of epithelial cells. Part of the iron destined for metabolism in other tissues is transported across the basolateral membrane of the cell and binds to transferrin, the main iron transport protein in the blood. In cells, iron is deposited in the form of ferritin, a complex of the protein apoferritin with iron. Accumulations of decayed ferritin molecules are hemosiderin. Approximately one third of the body's iron stores are in the form of hemosiderin, which is increased in iron-related diseases.

With hemochromatosis, the absorption of iron in the digestive tract increases to 3.0-4.0 mg. Thus, within 1 year, its excess amount deposited in the cells of the liver, pancreas, heart and other organs and tissues is approximately 1 g. Ultimately, the intra- and extracellular pools of the body become oversaturated with iron, which allows free iron to enter into toxic intracellular reactions. Being a strong redox substance, iron creates free hydroxyl radicals, which, in turn, destroy the macromolecules of lipids, proteins and DNA.

Increased accumulation of iron in the liver is characterized by:

• Fibrosis and cirrhosis of the liver with the initial predominant accumulation of iron in parenchymal cells, to a lesser extent - in stellate reticuloendotheliocytes.
• Deposition of iron in other organs, including the pancreas, heart, pituitary gland.
• Increased absorption of iron, which leads to its adsorption and accumulation.

The disease is associated with the so-called missense mutations, i.e. mutations that cause a change in the meaning of the codon and lead to a stop in protein biosynthesis.

The genetic nature of PHC was confirmed by M. Simon et al. in 1976, who revealed in representatives of the European population a close association of the disease with certain antigens of the major histocompatibility complex. For clinical expression, the patient must have two PHC alleles (homozygosity). The presence of one common HLA haplotype with the patient indicates heterozygous carriage of the PHC allele. Such individuals may have indirect signs indicating an increased iron content in the body, and the absence of clinically significant symptoms. Heterozygous gene carriage prevails over homozygous. If both parents are heterozygotes, a pseudo-dominant type of inheritance is possible. In heterozygotes, iron absorption is usually somewhat increased, a slight increase in serum iron is detected, but life-threatening trace element overload is not observed. At the same time, if heterozygotes suffer from other diseases accompanied by iron metabolism disorders, then clinical and morphological signs of the pathological process may appear.

The close relationship of the disease with HLA antigens made it possible to localize the gene responsible for PHC, located on the short arm of chromosome 6, near the A locus of the HLA system and associated with the A3 allele and the A3 B7 or A3 B14 haplotypes. This fact served as the basis for research aimed at its identification.

Hereditary hemochromatosis was originally considered a simple monogenic disease. Currently, by gene defect and clinical picture There are 4 forms of PHC:

• classic autosomal recessive HFE-1;
• juvenile HFE-2;
• HFE-3 associated with a mutation in the type 2 transferrin receptor;
• autosomal dominant hemochromatosis HFE-4.

Identification of the HFE gene (associated with the development of hemochromatosis) was important point in understanding the essence of the disease. The HFE gene encodes the structure of a protein consisting of 343 amino acids, the structure of which is similar to the molecule of the MHC class I system. Mutations in this gene have been identified in persons suffering from hemochromatosis. Carriers of the C282Y allele in the homozygous state among ethnic Russians are at least 1 per 1000 people. The role of HFE in iron metabolism is evidenced by the interaction of HFE with the transferrin receptor (TfR). The association of HFE with TfR reduces the affinity of this receptor for iron-bound transferrin. With the C282Y mutation, HFE is not able to bind to TfR at all, and with the H63D mutation, affinity for TfR decreases to a lesser extent. The three-dimensional structure of HFE was studied using X-ray crystallography, which gave reason to establish the nature of the interaction between HFE and the 2m light chain, as well as to determine the localization of mutations characteristic of hemochromatosis.

The C282Y mutation leads to a break in the disulfide bond in a domain that is important in the formation of the correct spatial structure of the protein and its binding to 2m. The largest number The HFE protein is produced in the deep crypts of the duodenum. Normally, the role of the HFE protein in krypton cells is to modulate transferrin-bound iron uptake. In a healthy person, an increase in serum iron levels leads to an increase in its uptake by deep crypt cells (a process mediated by TfR and modulated by HFE). The C282Y mutation can disrupt TfR-mediated iron uptake by cryptic cells and thus generate a false signal of the presence of low iron in the body.

Due to the decrease in intracellular iron content, differentiating enterocytes migrating to the top of the villi begin to produce an increased amount of DMT-1, resulting in increased iron uptake. The main link in the pathogenesis is a genetic defect in the enzyme systems that regulate the absorption of iron in the intestine during its normal intake with food. A genetic link with the HLA-A system has been proven. The study of linkage disequilibrium using these markers showed the relationship of hemochromatosis with Az, B7, Bt4, D6 Siosh D6 S126O.

Further studies in this direction and haplotype analysis suggest that the gene is located between D6 S2238 and D6 S2241. The putative gene for hemochromatosis is homologous to HLA, and the mutation appears to affect a functionally important region. The gene that controls the iron content in the body is located at the A3HLA locus on the 6th chromosome. This gene encodes the structure of a protein that interacts with the transferrin receptor and reduces the affinity of the receptor for the transferrin iron complex. Thus, the mutation of the HFE gene disrupts transferrin-mediated iron uptake by duodenal enterocytes, resulting in a false signal about the presence of low iron in the body, which, in turn, leads to increased production of the iron-binding protein DCT-1 in the villi of enterocytes and how the result is an increased uptake of iron.

Potential toxicity is explained by its ability, as a variable valence metal, to trigger valuable free radical reactions leading to toxic damage to organelles and genetic structures of the cell, increased collagen synthesis and the development of tumors. Heterozygotes show a slight increase in serum iron but no excess iron accumulation or tissue damage.

However, this can happen if heterozygotes also suffer from other diseases accompanied by iron metabolism disorders.

Secondary hemochromatosis often develops against the background of blood diseases, tardive cutaneous porphyria, frequent blood transfusions, and taking iron-containing drugs.

Symptoms of Hemochromatosis:

Peculiarities clinical manifestations:

Clinical manifestations of the disease develop after the onset of adulthood, when iron stores in the body reach 20-40 g or more.

There are three stages in the development of the disease:

• without the presence of iron overload with a genetic predisposition;
• iron overload without clinical manifestations;
• clinical stage.

The onset of the disease is gradual. In the initial stage, for a number of years, complaints of severe weakness, fatigue, weight loss, and a decrease in sexual function in men predominate. Often there is pain in the right hypochondrium, joints due to chondrocalcinosis of large joints, dryness and atrophic changes in the skin, testicles.

The advanced stage of the disease is characterized by the classic triad. pigmentation of the skin, mucous membranes, cirrhosis of the liver and diabetes.

Pigmentation is one of the most common early symptoms hemochromatosis. Its severity depends on the duration of the process. A bronze, smoky skin tone is more visible on exposed parts of the body (face, neck, HANDS), on previously pigmented areas, in the armpits, on the genitals.

In most patients, iron is primarily deposited in the liver. Liver enlargement is observed in almost all patients. The consistency of the liver is dense, the surface is smooth, in some cases its pain is given to palpation. Splenomegaly is detected in 25-50% of patients. Extrahepatic signs are rare. Pair diabetes occurs in 80% of patients. He is often insulin dependent.

Endocrine disorders are observed in the form of hypofunction of the pituitary, epiphysis, adrenal glands, thyroid gland(1/3 of patients) gonads. Different kinds endocrinopathies occur in more than 80% of patients. The most common form of pathology is diabetes mellitus.

The deposition of iron in the heart with PCH is observed in 90-100% of cases, however, clinical manifestations of heart damage are found only in 25-35% of patients. Cardiomyopathy is accompanied by an increase in the size of the heart, rhythm disturbances, and the gradual development of refractory heart failure.

Perhaps a combination of hemochromatosis with arthropathy, chondrocalcinosis, osteoporosis with calciuria, neuropsychiatric disorders, tuberculosis, tardive cutaneous porphyria.

Allocate latent (including patients with a genetic predisposition and minimal iron overload), with severe clinical manifestations, and terminal hemochromatosis. Hepatopathic, cardiopathic, endocrinological forms are more common: respectively, slowly progressive, rapidly progressive, and a form with a fulminant course.

The latent stage of PHC is observed in 30-40% of patients, which is detected during a family genetic examination of patients' relatives or during population screening. Some of these persons of the older age group have minimal symptoms in the form of slight weakness, increased fatigue, a feeling of heaviness in the right hypochondrium, pigmentation of the skin in open areas of the body, decreased libido, and slight hepatomegaly.

The stage of advanced clinical manifestations is characterized by the presence of asthenovegetative syndrome, abdominal pain, sometimes quite intense, arthralgia, decreased libido and potency in 50% of men and amenorrhea in 40% of women. In addition, weight loss, cardialgia and palpitations may be observed. An objective examination reveals hepatomegaly, melasma, pancreatic dysfunction (insulin-dependent diabetes mellitus).

In the terminal stage of HCH, signs of decompensation of organs and systems are observed in the form of the formation of portal hypertension, the development of hepatocellular, as well as right and left ventricular heart failure, diabetic coma, exhaustion. The causes of death of such patients, as a rule, are bleeding from varicose veins of the esophagus, hepatocellular and heart failure, aseptic peritonitis, diabetic coma.

In such patients, there is a predisposition to the development of a tumor process (the risk of its development in people over 55 years of age is 13 times higher than in the general population).

Juvenile hemochromatosis is a rare form of the disease that occurs at a young age (15-30 years) and is characterized by severe iron overload, accompanied by symptoms of liver and heart damage.

Diagnosis of Hemochromatosis:

Diagnostic features:

Diagnosis is based on multiple organ lesions, cases of the disease in several members of the same family, elevated iron levels, iron excretion in the urine, high concentrations of transferrin, ferritin in the blood serum. Diagnosis is likely in association with diabetes mellitus, cardiomyopathy, hypogonadism, and typical skin pigmentation. Laboratory criteria are hyperferremia, an increase in the transferrin saturation index (more than 45%). Sharply increase the level of ferritin in the blood serum, excretion of iron in the urine (desferal test). After intramuscular injection 0.5 g of desferal iron excretion increases to 10 mg / day (at a rate of 1.5 mg / day), the coefficient of NTJ (iron / FBC) increases. With the introduction of genetic testing into practice, the number of people with hemochromatosis without clinical signs iron overload. Conduct a study for the presence of mutations C282Y/H63D in the risk group for the development of iron overload. If the patient is a homozygous C282Y/H63D carrier, the diagnosis of hereditary hemochromatosis can be considered established.

Among non-invasive research methods, the deposition of a trace element in the liver can be determined using MRI. The method is based on a decrease in the intensity of the signal of the liver overloaded with iron. In this case, the degree of signal intensity decrease is proportional to iron reserves. The method allows you to determine the excess deposition of iron in the pancreas, heart and other organs.

Liver biopsy shows abundant iron deposition. positive reaction Perls. In a spectrophotometric study, the iron content is more than 1.5% of the dry mass of the liver. Importance is given to the quantitative measurement of the level of iron in liver biopsy specimens by atomic absorption spectrometry, followed by the calculation of the hepatic iron index. The index represents the ratio of iron concentration in the liver (in µmol/g dry weight) to the age of the patient (in years). With PHC already on early stages this indicator is equal to or exceeds 1.9-2.0 and does not reach the specified value in other conditions characterized by hemosiderosis of the liver.

In the latent stage of the disease functional tests liver practically do not change, and according to histological examination, hemosiderosis of the 4th degree, fibrosis of the portal tracts without pronounced signs of inflammatory infiltration are observed.

At the stage of advanced clinical manifestations, histological changes in the liver usually correspond to pigmented septal or small nodular cirrhosis with massive deposits of hemosiderin in hepatocytes and less significant in macrophages, epithelium bile ducts.

Histological examination in the terminal stage of the disease reveals a picture of generalized hemosiderosis with damage to the liver (by the type of mono- and multilobular cirrhosis), heart, pancreas, thyroid, salivary and sweat glands, adrenal glands, pituitary gland and other organs.

Iron overload has been observed in a number of congenital or acquired conditions from which HHC must be differentiated.

Classification and causes of the development of the state of iron overload:

• Familial or congenital forms of hemochromatosis:
  • Congenital HFE-associated hemochromatosis:
    • homozygous for C282Y;
    • mixed heterozygosity for C282Y/H63D.
  • congenital HFE-non-associated hemochromatosis.
  • Juvenile hemochromatosis.
  • Iron overload in newborns.
  • Autosomal dominant hemochromatosis.
• Acquired iron overload:
  • Hematological diseases:
    • anemia due to iron overload;
    • thalassemia major;
    • sideroblastic anemia;
    • chronic hemolytic anemia.
• Chronic liver diseases:
  • hepatitis C;
  • alcoholic liver disease;
  • nonalcoholic steatohepatitis.

The disease must also be differentiated from blood pathology (thalassemia, sideroblastic anemia, hereditary atransferrinemia, microcytic anemia, tardive cutaneous porphyria), liver diseases (alcoholic liver damage, chronic viral hepatitis, non-alcoholic steatohepatitis).

Treatment of Hemochromatosis:

Features of the treatment of hemochromatosis:

A diet rich in proteins is shown, without foods containing iron.

Most accessible way removal of excess iron from the body are bloodletting. Usually 300-500 ml of blood is removed with a frequency of 1-2 times a week. The number of phlebotomies is calculated depending on the level of hemoglobin, blood hematocrit, ferritin, and the amount of excess iron. This takes into account that 500 ml of blood contains 200-250 mg of iron, mainly in the hemoglobin of erythrocytes. Bleeding continues until the patient develops mild anemia. A modification of this extracorporeal technique is cytapheresis (CA) (removal of the cellular part of the blood with the return of autoplasma in a closed circuit). In addition to the mechanical removal of blood cells, CA has a detoxifying effect and helps to reduce the severity of degenerative-inflammatory processes. Each patient undergoes 8-10 sessions of CA with a further transition to maintenance therapy using CA or hemoexfusions in the amount of 2-3 sessions for 3 months.

Drug treatment is based on the use of deferoxamine (desferal, desferin), 10 ml of a 10% solution intramuscularly or intravenously by drip. The drug has a high specific activity towards Fe3+ ions. At the same time, 500 mg of Desferal are able to remove 42.5 mg of iron from the body. The duration of the course is 20-40 days. At the same time, cirrhosis, diabetes mellitus and heart failure are treated. The frequently observed anemic syndrome in patients with HCH in the presence of excessive iron content in the liver tissue limits the use of efferent therapy. Our clinic has developed a scheme for the use of recombinant erythropoietin against the background of CA. The drug promotes increased utilization of iron from the body's depot, due to which there is a decrease in the total reserves of the microelement, an increase in hemoglobin levels. Recombinant erythropoietin is administered at a dose of 25 μg/kg of body weight against the background of CA sessions conducted 2 times a week for 10-15 weeks.

Forecast:

The forecast is determined by the degree and duration of overloads.

The course of the disease is long, especially in the elderly. Timely therapy prolongs life by several decades. Survival for 5 years in treated patients is 2.5-3 times higher than in untreated patients. The risk of developing HCC in patients with HCC in the presence of liver cirrhosis increases by 200 times. The most common cause of death is liver failure.

Which doctors should you contact if you have Hemochromatosis:

• Gastroenterologist
• Nutritionist

Are you worried about something? Do you want to know more detailed information about Hemochromatosis, its causes, symptoms, methods of treatment and prevention, the course of the disease and diet after it? Or do you need an inspection? You can book an appointment with a doctor– clinic Eurolaboratory always at your service! The best doctors examine you, study external signs and help identify the disease by symptoms, advise you and provide needed help and make a diagnosis. you also can call a doctor at home. Clinic Eurolaboratory open for you around the clock.

How to contact the clinic:
Phone of our clinic in Kyiv: (+38 044) 206-20-00 (multichannel). The secretary of the clinic will select a convenient day and hour for you to visit the doctor. Our coordinates and directions are indicated. Look in more detail about all the services of the clinic on her.

(+38 044) 206-20-00

If you have previously performed any research, be sure to take their results to a consultation with a doctor. If the studies have not been completed, we will do everything necessary in our clinic or with our colleagues in other clinics.

You? You need to be very careful about your overall health. People don't pay enough attention disease symptoms and do not realize that these diseases can be life-threatening. There are many diseases that at first do not manifest themselves in our body, but in the end it turns out that, unfortunately, it is too late to treat them. Each disease has its own specific signs, characteristic external manifestations - the so-called disease symptoms. Identifying symptoms is the first step in diagnosing diseases in general. To do this, you just need to several times a year be examined by a doctor not only to prevent a terrible disease, but also to maintain a healthy spirit in the body and the body as a whole.

If you want to ask a doctor a question, use the online consultation section, perhaps you will find answers to your questions there and read self care tips. If you are interested in reviews about clinics and doctors, try to find the information you need in the section. Also register on the medical portal Eurolaboratory to be constantly up to date with the latest news and information updates on the site, which will be automatically sent to you by mail.

Other diseases from the group Diseases of the gastrointestinal tract: