Increased iron content in the body hemosiderosis hemochromatosis. Hemochromatosis (Bronze diabetes, Pigmented cirrhosis). Features of the treatment of hemochromatosis

• What is Hemochromatosis
• What provokes Hemochromatosis
• Symptoms of Hemochromatosis
• Diagnostics of the Hemochromatosis
• Treatment of Hemochromatosis
• Which doctors should you contact if you have Hemochromatosis?

What is Hemochromatosis

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

What provokes Hemochromatosis

The disease was first described by M. Troisier in 1871 as a symptom complex characterized by diabetes mellitus, skin pigmentation, liver cirrhosis associated with the accumulation of iron in the body. In 1889, Reclinghausen coined the term "hemochromatosis", reflecting one of the features of the disease: the unusual coloration of the skin and internal organs. It was found that iron initially 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 perception of PHC as a rare disease. The prevalence of the PHC gene is 0.03-0.07% - so, until recently, there were 3-8 cases per 100 thousand of the population. 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 is on average 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 in the composition of hemoglobin, myoglobin, catalase and other respiratory-bix pigments or enzymes. Iron reserves are 0.5 g, part of them are in the liver, but they are not visible during histological examination for 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 mainly in the upper small intestine and is an active process in which iron can be transported further against a concentration gradient. However, the transfer mechanisms are unknown.

In the cells of the intestinal mucosa, iron is in the cytosol. Some of it is bound and stored in the form of 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 transport protein of iron in the blood. In cells, iron is deposited in the form of ferritin, a complex of the protein apoferritin with iron. Clusters of decayed ferritin molecules are hemosiderin. Approximately one third of the body's iron stores is in the form of hemosiderin, the amount of which increases in diseases associated with excess iron accumulation.

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 about 1 g. Ultimately, the intra- and extracellular pools of the body become supersaturated with iron, which allows the free gland to enter into toxic intracellular reactions. As a strong redox agent, iron creates free hydroxyl radicals, which in turn destroy macromolecules of lipids, proteins and DNA.

An increased accumulation of iron in the liver is characterized by:

• Fibrosis and cirrhosis of the liver with an initial predominant accumulation of iron in parenchymal cells, to a lesser extent in stellate reticuloendotheliocytes.
• Iron deposition in other organs, including the pancreas, heart, and 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 the arrest of 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 main histocompatibility complex. For clinical expression, the patient must have two alleles of PHC (homozygosity). The presence of one common HLA haplotype with the patient indicates the heterozygous carriage of the PHC allele. In such individuals, indirect signs may be found that indicate an increased content of iron in the body, and the absence of clinically significant symptoms. Heterozygous carriage of a gene predominates over homozygous one. If both parents are heterozygous, a pseudo-dominant type of inheritance is possible. In heterozygotes, iron absorption is usually slightly increased, a slight increase in serum iron is detected, but there is no life-threatening trace element overload. At the same time, if heterozygotes suffer from other diseases accompanied by disorders of iron metabolism, then clinical and morphological signs of a 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 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, according to the gene defect and the clinical picture, 4 forms of PHC are distinguished:

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

The identification of the HFE gene (associated with the development of hemochromatosis) was an 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 MHC class I molecule. In persons suffering from hemochromatosis, mutations in this gene have been identified. Carriers of the C282Y allele in a 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 generally unable to bind to TfR, and with the H63D mutation, the affinity for TfR decreases to a lesser extent. The three-dimensional structure of HFE was investigated using X-ray crystallography, which made it possible to establish the nature of the interaction between HFE and the light chain 2m, as well as to determine the localization of mutations characteristic of hemochromatosis.

The C282Y mutation leads to the breaking of the disulfide bond in the domain, which is important in the formation of the correct spatial structure of the protein and its binding to 2m. The largest amount of the HFE protein is produced in the deep crypts of the duodenum. Normally, the role of the HFE protein in cryptone cells is to modulate transferrin-associated 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 crypt cells and, thus, generate a false signal about the presence of low iron in the body.

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

Further studies in this direction and analysis of haplotypes suggest that the gene is located between D6 S2238 and D6 S2241. The putative hemochromatosis gene 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 chromosome 6. This gene encodes the structure of a protein that interacts with the transferrin receptor and reduces the receptor's affinity for the transferring-iron complex. Thus, the mutation of the HFE gene disrupts the transferrin-mediated capture of iron by the enterocytes of the duodenum, as a result of which a false signal is formed about the presence of a low iron content in the body, which, in turn, leads to an increased production of the iron-binding protein DCT-1 in the villi of enterocytes and how the consequence is an increased capture of iron.

Potential toxicity is explained by its ability, as a metal with variable valence, 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 levels, but do not show excessive iron accumulation or tissue damage.

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

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

Symptoms of Hemochromatosis

Features of 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;
• stage of clinical manifestations.

The onset of the disease is gradual. In the initial stage, for a number of years, complaints of pronounced weakness, fatigue, weight loss, and decreased 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 and testicles.

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

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

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

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

Iron deposition in the heart with PHC 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.

A combination of hemochromatosis with arthropathy, chondrocalcinosis, osteoporosis with calciuria, neuropsychiatric disorders, tuberculosis, and tardive cutaneous porphyria is possible.

Allocate latent (including patients with a genetic predisposition and minimal iron overload), with severe clinical manifestations, and terminal hemochromatosis. More often there are hepatopathic, cardiopathic, endocrinological forms: respectively, slowly progressing, rapidly progressing and a form with a fulminant course.

The latent stage of PHC is observed in 30-40% of patients, which is detected during 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 occur. An objective examination reveals hepatomegaly, melasma, dysfunction of the pancreas (insulin-dependent diabetes mellitus).

In the terminal stage of PHC, there are signs of decompensation of organs and systems in the form of portal hypertension, development of hepatocellular, as well as right and left ventricular heart failure, diabetic coma, and 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 persons 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.

Diagnostics of the Hemochromatosis

Diagnostic features:

Diagnosis is based on multiple organ lesions, cases of the disease in several members of the same family, increased iron content, urinary iron excretion, high transferrin concentration, and serum ferritin. The diagnosis is likely when combined with diabetes mellitus, cardiomyopathy, hypogonadism, and typical skin pigmentation. The laboratory criteria are hyperferremia, an increase in the transferrin saturation index (more than 45%). The level of ferritin in the blood serum and the excretion of iron in the urine (desferal test) sharply increase. After intramuscular injection of 0.5 g of desferal, the release of iron increases to 10 mg / day (at a rate of 1.5 mg / day), the NTI coefficient (iron / TIBC) increases. With the introduction of genetic testing into practice, the number of people with hemochromatosis without clinical signs of iron overload has increased. A study is carried out for the presence of C282Y / H63D mutations in the risk group for the development of iron overload. If the patient is a homozygous carrier of C282Y / H63D, 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 signal intensity of the liver overloaded with iron. In this case, the degree of decrease in the signal intensity is proportional to the iron stores. The method allows you to determine the excessive deposition of iron in the pancreas, heart and other organs.

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

In the latent stage of the disease, liver function tests practically do not change, and according to histological studies, grade 4 hemosiderosis, 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, bile duct epithelium.

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

Iron overload is seen in a number of congenital or acquired conditions with which PHC must be differentiated.

Classification and reasons for the development of an iron overload condition:

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

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

Treatment of Hemochromatosis

Features of the treatment of hemochromatosis:

Shown is a protein-rich diet, no iron-rich foods.

The most affordable way to remove excess iron from the body is bloodletting. Usually, 300-500 ml of blood is removed at a frequency of 1-2 times a week. The number of bloodletting is calculated depending on the level of hemoglobin, blood hematocrit, ferritin, and the amount of excess iron. It is taken into account that 500 ml of blood contains 200-250 mg of iron, mainly in the composition of erythrocyte hemoglobin. Bloodletting 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 corpuscles, 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 supportive therapy using CA or hemoexfusion 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 drip. The drug has a high specific activity for 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 PHC in the presence of excess iron content in the liver tissue limits the use of efferent therapy. In our clinic, a scheme for the use of recombinant erythropoietin against the background of CA has been developed. 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 trace element, an increase in the level of hemoglobin. Reombinant 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 congestion.

The course of the disease is long, especially in the elderly. Timely therapy prolongs life by several decades. The survival rate for 5 years in treated patients is 2.5-3 times higher than in untreated patients. The risk of developing HCC in patients with PHC in the presence of liver cirrhosis increases 200 times. Most often, death occurs due to liver failure.

Hemochromatosis is a hereditary disease that affects almost all systems and organs. This is a severe pathology, which is also called bronze diabetes or pigmentary cirrhosis.

Among genetic abnormalities, this disease is recognized as one of the most common. The maximum number of cases was recorded in the Nordic countries.

Statistics and medical history

A mutated gene is responsible for the development of the disease, which 5% of the population has, but the disease develops in only 0.3%. The prevalence in men is 10 times higher than in women. In most patients, the first symptoms appear at the age of 40-60 years.

The disease code according to ICD-10 is U83.1.

For the first time information about the disease appeared in 1871. M. Troisier was described as a complex with symptoms of diabetes mellitus, cirrhosis, skin pigmentation.

In 1889, the term "hemochromatosis" was introduced. It reflects one of the features of the disease: the dermis and internal organs acquire an unusual color.

Reasons for development

Primary hereditary hemochromatosis is an autosomal recessive transmission. It is based on HFE mutations. This gene is located on the short arm of chromosome 6.

The defect leads to a violation of the capture of iron by the cells of the duodenum. Therefore, a false signal appears about the occurrence of iron deficiency in the body.

This leads to an increase in the formation of iron-binding protein and an increase in the absorption of iron in the intestine. Subsequently, pigment is deposited on many organs, followed by the death of active elements and the development of sclerotic processes.

The disease can manifest itself at any age. There are certain prerequisites:

• Metabolic disorders. Often, the disease is detected against the background of cirrhosis of the liver or during bypass surgery.
• Diseases of the liver. Especially if they are of a viral nature, for example, hepatitis B and C, which have not been treated for more than 6 months.
• Overgrowth of liver tissue with fat.
• Availability or.
• The introduction of specific intravenous drugs that provoke an increase in the concentration of iron.
• Permanent hemodialysis.

Forms of the disease

There are three types of ailment:

• Hereditary (primary). In the primary case, we are talking about the mutation of genes responsible for iron metabolism. This form is the most common. A link has been established between hereditary hemochromatosis and congenital enzyme defects that lead to iron accumulation.

Photo of diagnosis of hereditary hemochromatosis

• Neonatal appears in newborn babies. The reasons for the development of such a pathology have not yet been clarified.
• Secondary develops against the background of other diseases that are associated with blood circulation and skin problems. It develops on the background of taking a large number of preparations containing iron.

The latter type can be post-transfusion, alimentary, metabolic and mixed origin.

Stages

There are three main stages:

• First. Disorders in iron metabolism are observed, but its amount remains below the permissible level.
• Second. Excessive accumulation of iron by the body occurs. There are no special clinical signs, but thanks to laboratory research methods, it becomes possible to quickly establish a deviation from the norm.
• Third. All symptoms of the disease begin to progress. The disease affects most organs and systems.

Symptoms of hemochromatosis

The disease manifests itself most clearly in people of mature age, when the content of total iron reaches critical values.

Depending on the prevailing symptoms, several forms of hemochromatosis differ:

• liver,
• hearts,
• endocrine system.

First, the patient complains of increased fatigue, decreased libido. Not very strong ones may appear. Gradually, the skin becomes drier, disorders appear in large joints.

In the expanded stage, a symptom complex is formed, represented by a change in skin color to a bronze tint, the development of cirrhosis of the liver, diabetes mellitus. Pigmentation mainly affects the face, upper hand, navel and nipples. Hair gradually falls out.

Excessive accumulation of iron in tissues and organs leads to testicular atrophy in men. The limbs become swollen, and a sharp weight loss appears.

Complications

The liver ceases to cope with its functions. Therefore, it begins to take part less in digestion, neutralization, and metabolism. There are violations of the heart rate, a decrease in the contractility of the heart muscle.

The body becomes predisposed to other diseases, since the immune system cannot cope with the stress.

Common complications are:

• ... There is a death of part of the heart area due to circulatory disorders. Pathology can occur against the background of heart failure.
• Diabetic and. Due to toxins, brain damage occurs, which accumulate in diabetes mellitus.
• The appearance of tumors in the liver.

If bacteria enter the bloodstream, sepsis can develop. It leads to severe intoxication of the whole organism and a significant deterioration in the patient's condition. As a result of sepsis, the likelihood of death is high.

Some patients have hypogonadism as a complication. This is a disease associated with a decrease in the production of sex hormones. This pathology leads to sexual dysfunction.

Diagnostics

Diagnostic measures are prescribed for multiple organ lesions and for the disease of several members of the same family. Attention is paid to the age of onset of the disease.

With a hereditary form, symptoms appear at the age of 45-50 years. With an earlier appearance of signs, they speak of hemochromatosis of the second type.

Among non-invasive methods, it is often used. There is a decrease in the signal intensity of the liver, which is overloaded with iron. Moreover, its strength depends on the amount of trace element.

When there is an abundant deposition of Fe, giving a positive Perls reaction. With a spectrophotometric study, it can be established that the iron content is more than 1.5% of the dry mass of the liver. The staining results are assessed visually depending on the percentage of stained cells.

Additionally, they can carry out:

• X-ray of the joints,
• EchoCG.

Blood test

A complete blood count is not indicative. It is needed only to exclude anemia. The most frequently rented, which is shown:

1. Increase in bilirubin above 25 μmol per liter.
2. Increase in ALAT above 50.
3. With diabetes mellitus, the amount of glucose in the blood increases 5.8.

If you suspect hemochromatosis, a special scheme is used:

• First, a transferrin concentration test is performed. The specificity of the test is 85%.
• Ferritin dosing test. If the result is positive, then proceed to the next steps.
• Phlebotomy. This is a medical and diagnostic method aimed at extracting a certain amount of blood. It aims to remove 3 gr. gland. If after this the patient becomes better, then the diagnosis is confirmed.

Treatment

Therapeutic methods depend on the characteristics of the clinical picture. It is imperative to follow a diet in which there is no food with iron and other substances that contribute to the absorption of this trace element.

Therefore, under a strict ban:

• kidney and liver dishes,
• alcohol,
• flour products,
• seafood.

In small quantities, you can eat meat, foods fortified with vitamin C. It is possible to use coffee and tea in the diet, since tannins slow down the absorption and accumulation of iron.

Phlebotomy, described just above, also has a therapeutic effect. The duration of bloodletting for medicinal purposes is at least 2 years, until ferrin is reduced to 50 units. Simultaneously with this, the dynamics of hemoglobin is monitored.

Cytophoresis is sometimes used. The essence of the method consists in passing blood through a closed cycle. In this case, the serum is purified. After that, the blood returns. To obtain the desired result, 10 procedures are carried out in one cycle.

For treatment, chelators are used, which help the gland to be excreted from the body faster. Such an effect is carried out only under the watchful guidance of a doctor, since with prolonged use or use without control, there is a clouding of the lens of the eye.

If hemochromatosis is complicated by the growth of a malignant tumor, then surgical treatment is prescribed. With progressive cirrhosis, liver transplantation is prescribed. Arthritis is treated with joint plastic surgery.

Forecast and prevention

When a disease appears, to prevent complications, you need:

1. Follow a diet.
2. Take iron-binding medications.

If there is no hemochromatosis, but there are hereditary preconditions, then it is necessary to strictly follow the doctor's recommendations when taking iron preparations. Prevention also boils down to family screening and early detection of the onset of the disease.

The disease is dangerous and has a progressive course. With timely therapy, life can be extended by several decades.

In the absence of medical care, survival is rarely more than 5 years. In the presence of complications, the prognosis is poor.

Video lecture about hemochromatosis of the liver:

Hemochromatosis is a disease that affects the metabolism of iron, which causes excess iron in the body. Find out what causes it, symptoms and treatment.

There is no doubt that the liver is one of the most important organs in our body. Among its main functions, one can mention the storage and release of sugar in the blood, the synthesis of glycogen, the processing of alcoholic beverages and various drugs, the elimination of impurities from the blood ...

However, there are a number of liver diseases that can clearly affect the liver, especially directly. A good example is hemochromatosis, a disease that can be hereditary or acquired.

What is hemochromatosis?

Hemochromatosis is a change characterized by poor metabolism of iron in our body. Needless to say, it is an essential component of our body if we want all of our organs to function properly. It is estimated that the correct amount of iron in the blood should be at least about 4 or 5 grams, the amount that is released from hemoglobin.

However, this condition is characterized by the fact that the body is unable to break down this element and therefore causes an excessive increase in the level of iron throughout the digestive tract. This is something that can have a very negative impact on our health and especially on the functioning of the liver.

Hemochromatosis is a disease that occurs in people of all ages. It can affect about one in 200-300 people and is much more common in men because women have other ways to get rid of iron through pregnancy.

What are the causes of hemochromatosis?

Now that we already know what hemochromatosis consists of, we are going to explain what its causes are:

• Excessive consumption of wine. This alcoholic beverage is characterized by the presence of high doses of iron. Therefore, if it is taken in too much, it is possible that the person is suffering from hemochromatosis.
• Hepatitis C. This liver virus can also cause an increase in the level of iron in the blood.
• Blood transfusion. When a person receives multiple transfusions for any reason, this process also causes iron deposits to begin to accumulate.
• Deficiency in the production of transferrin. Transferrin is a protein that is responsible for transporting all iron through the body. However, problems arise when a person is unable to secrete this protein naturally, causing a clear case of hemochromatosis.

Symptoms of hemochromatosis

The symptoms of hemochromatosis can vary depending on how advanced the disease is. Therefore, it is very important to determine it as soon as possible. Among the most common symptoms are:

• Liver damage: One of the most common symptoms of hemochromatosis is what is known as hepatomegaly. This means that the left side of the liver is inflamed, which can subsequently cause ascites, edema, and even jaundice.
• Excess iron can also build up through various heart muscles, which can subsequently cause mild heart failure. Extreme tiredness and swelling of the legs are prominent symptoms of this condition.
• Hyperpigmentation of the skin: Most cases of hemochromatosis usually translate later in cases of hyperpigmentation of the skin to very dark tones. It's also normal to see pictures of baldness or hair loss.

Types of hemochromatosis

As stated at the beginning of this post, there are two different types of hemochromatosis: one hereditary (the most common) and one acquired. Below we will find out the main differences.

Hereditary hemochromatosis

Hereditary hemochromatosis is a genetic disorder of the autosomal recessive type (or recessive inheritance), which means that it must be inherited from the father and mother to manifest it; that is, both parents must carry the gene.

It is estimated that every 20-25 people carry a gene, which means that we have a hereditary liver disease that is very common.

In the case of hereditary hemochromatosis, two mutations have been identified in the HFE protein genes, known as C282Y and H63D. Studies show that in Europe, it is estimated that 60 to 100% of affected patients inherit the C282Y gene from both parents (homozygous C282Y) or inherit the H63D gene from one and the C282Y gene from the other (double heterozygotes).

Acquired hemochromatosis

Also known as secondary hemochromatosis, it is caused by a wide variety of disorders and conditions, and there is no single or specific cause that leads to increased iron deposits in the body.

Among the reasons that most often cause the appearance of this hemochromatosis, you can mention:

• Liver diseases such as alcoholic liver disease or hepatitis C.
• Chronic alcohol consumption affecting the liver.
• Performing multiple blood transfusions.
• Congenital transferrin deficiency.
• Porphyria cutaneous tarda.
• Neonatal hemochromatosis.
• Aceruloplasminemia.
• Excessive iron intake

What treatment is there for hemochromatosis?

Since hemochromatosis is characterized by too high a dose of iron in our body, it is obvious that it will be necessary to reduce the levels of this component. To do this, you must take into account the following signs:

• Reducing alcohol consumption. The consumption of certain beverages, such as red or rosé wine, can cause hemochromatosis. Therefore, it is strongly recommended that you stop taking them from the moment the first symptoms appear.
• Avoid white fish and seafood. Fish is also an inexhaustible source of iron. Therefore, you will need to stop taking it for a while to lower your iron levels. The same goes for shellfish or vitamin supplements that contain iron or vitamin C.
• Stay away from utensils made of iron. And the fact is that processing or manipulating it can lead to the fact that later we borrow this element by accident.

Hemochromatosis (bronze diabetes, pigmentary cirrhosis), being a hereditary disease, is transmitted to the recipient by recessive genes. According to statistics, about 0.33% of people are susceptible to this disease and about 10% are carriers of its genome. The clinical picture and symptoms were first described in 1871. There were signs of diabetes mellitus, cirrhosis of the liver, an unusual bronze color of the skin. Several years later, the term "hemochromatosis" was introduced, which characterizes the main symptoms of the disease.

It also turned out that men are susceptible to this disease much more women. On average, there is 1 woman for every 20 sick men. This is due to the presence of menstrual flow in women, due to which the body is freed from excess iron. Hemochromatosis is rare at a young age. Most often, persons from 40 years of age and above are on the list of those with this ailment.

The danger of this disease lies in its inconspicuousness. Most cases of diagnosis of hemochromatosis were noted already in the late stages of the development of the disease.

To date, there are two types of this disease: primary and secondary hemochromatosis. Both the first and the second type of the disease are difficult to diagnose. Primary is called true or idiopathic hemochromatosis, transmitted at the gene level. Secondary hemochromatosis is not a congenital disease and is a consequence of anemias of various etiologies, blood transfusions or improper treatment with iron preparations.

Secondary hemochromatosis also includes:

1. Post-transfusion (caused by long-term treatment of anemia with multiple blood transfusions);
2. Metabolic (associated with a violation of iron metabolism in the body);
3. Alimentary (excess intake of iron-containing foods).

In addition, neonatal hemochromatosis, diagnosed in newborns, is also isolated. The disease is characterized by metabolic disorders, which are often fatal. Often the only effective treatment for this disease is.

Pathogenesis

The pathogenesis of the disease is caused by the accumulation of excess iron in the body, primarily in the cells of the liver, spleen, myocardium, and pancreas. This leads to the appearance of a large number of free iron radicals, which begin to enter into chemical oxidation reactions with proteins, lipids, DNA, etc.

In a healthy person, normally, the iron content does not exceed 3-4 g, while in a patient with hemochromatosis it reaches 50 and more. This concentration is explained by a gene mutation, as a result of which the basic processes of metabolism and absorption of substances are disrupted. As a result, there is an excessive absorption of iron, leading to disease. For example, in a healthy person, about 1-2 mg of iron is absorbed in the gastrointestinal tract in one day, in a patient with hemochromatosis - up to 6 mg. Excess iron in cells binds to the protein apoferritin, forming ferritin, in one molecule of which there can be up to 4.5 thousand iron atoms. Elevated ferritin levels are often indicative of hemochromatosis.

Approximately one third of patients develop diabetes mellitus, with various complications (this is facilitated by dysfunction of the pancreas, associated with an excess of iron in it). Disorders in the work of the pituitary gland affect the functioning of the genitourinary system (testicular atrophy, impotence). In the overwhelming majority of cases, there are diseases of the cardiovascular system (various arrhythmias, conduction disorders, heart failure, etc.).

With hemochromatosis, the risk of infectious diseases (pneumonia, hepatitis, bronchitis) increases significantly, which is associated with phagocyte dysfunction.

A characteristic "companion" of hemochromatosis is arthropathy - joint damage. The disease is characterized by severe pain in the joints and ligaments, which is explained by increased calcium deposition.

When diagnosing all concomitant diseases, it is important to determine their etiology.

Symptoms

The clinical picture is very similar to other liver diseases, which greatly complicates the diagnosis. It is highly desirable to start treatment even before the first signs of the disease appear. Modern medicine has a fairly wide range of biochemical analyzes that can diagnose the disease at an early stage. However, if symptoms did appear before the diagnosis was made, in most cases they are characterized by the following:

• liver functions are impaired, there is an increase in its size, exacerbation of chronic diseases, which are much more difficult with hemochromatosis. The risk of developing cirrhosis and liver cancer;
• most patients complain of persistent weakness and fatigue;
• pigmentation, darkening of the skin, due to the accumulation of melanin pigment;
• in some cases, there are complaints of joint pain. Under the influence of free iron, calcium compounds are retained in the body, deposited in the joints of the fingers, knees, hands;
• weakening of immunity, susceptibility to various kinds of infections, viruses;
• hair loss.

If untreated, the disease usually becomes chronic and can cause:

• an increase in the concentration of sugar in the blood due to dysfunctions of the pancreas;
• disruptions of the menstrual cycle in women and weakening of potency in men, due to the destructive effects of iron on the sex glands;
• heart failure, arrhythmia, disturbances in the work of the conducting system caused by the accumulation of iron in the heart;
• various hormonal disruptions associated with disorders of the thyroid gland;
• hyperpigmentation of skin areas on the palms, in the armpits, in the places of old scars.

Diagnostics

Given the genetic nature of the disease, it is necessary to inquire about the presence of this disease in the patient's relatives. Particular attention should be paid to his brothers and sisters. Other liver diseases with similar symptoms, such as alcoholic cirrhosis, should also be ruled out. Taking blood for biochemical analysis in hemochromatosis usually reveals the following:

• iron levels are above normal;
• a high percentage of transferrin saturation with iron;
• ferritin levels are significantly increased.

The most informative method for diagnosing hemochromatosis is liver biopsy, as well as genetic studies to identify mutating genes. Computed tomography can help determine the level of iron accumulation in organs (most often in the liver and heart). In some cases, quantitative phlebotomy is used to diagnose hemochromatosis. To do this, the patient's blood is taken twice a week (in fact, bloodletting), after which the analyzes are compared. If a complete blood count shows anemia caused by blood loss, hemochromatosis is excluded.

Treatment

The need for and methods of treatment is determined by the doctor, depending on the severity of the disease, gender, age, complications, etc.

The decisive factor in effective control of the disease is its early diagnosis.

The most common treatment for hemochromatosis is venesection or phlebotomy. Usually, about 400 ml of blood is taken from the patient every week. This helps to normalize the level of iron in the body. Blood sampling is carried out exclusively in hospitals and under the supervision of medical staff. The frequency of procedures and the duration of the venesection course is determined by the doctor. Some patients are forced to donate blood throughout their lives.

A special diet also helps to normalize iron levels in the blood and liver. From the patient's diet, it is necessary to exclude foods rich in iron (fish, meat products, eggs, etc.).

Important: only a doctor should determine the form of the diet and its duration! An improperly selected diet can worsen the patient's condition.

Sometimes drugs are prescribed that bind iron and remove it from the body (for example, deferoxamine, B-desferal).

A prerequisite for the treatment of hemochromatosis is the rejection of alcohol. Alcohol aggravates the overall picture of the disease and leads to cirrhosis in almost 100% of cases.

Lack of proper treatment can lead to fatal consequences.

16565 0

Hereditary hemochromatosis Is a genetic disease in which iron accumulates in the human body. This is a fairly common hereditary disease among Europeans. According to American experts, 1 in 240-300 inhabitants of the region suffers from hereditary hemochromatosis.

Patients with hemochromatosis may not have any complaints, and their life expectancy may not differ from that of healthy people. Others develop severe symptoms of iron overload, including sexual dysfunction, heart failure, joint pain, cirrhosis of the liver, diabetes mellitus, general weakness, and darkening of the skin.

The normal iron content in the body should be between 3 and 4 grams. The total amount of iron in the body is regulated by specific absorption mechanisms. Our body loses about 1 milligram of iron daily through sweat and dead skin and intestinal cells. Women lose an average of 1 milligram more due to menstruation. The intestines of a healthy adult compensate for this loss daily by absorbing iron from food. When a person loses a lot of iron in the blood, its absorption in the intestines is enhanced. Normal balance is maintained, so there are no large deposits of iron in the body.

In people with hereditary hemochromatosis, the daily absorption of iron from the intestine is greater than the norm that the body needs. And since the human body cannot quickly release iron, this leads to the accumulation and deposition of iron in organs and tissues. With hereditary hemochromatosis, up to 20 grams of iron accumulates in the patient's body by the age of 40-50 - five times more than the norm!

Excess iron is deposited in the joints, liver, testicles, heart, which leads to damage to these organs and causes symptoms of hemochromatosis. Women may store iron more slowly because they experience iron losses during menstruation, pregnancy and lactation. Thus, in women, symptoms of organ damage develop on average 10 years later than in men.

The hereditary nature of hemochromatosis

Hereditary hemochromatosis is an autosomal recessive disorder. This means that a child is only likely to develop hemochromatosis if both of his parents had the gene for the disease. In contrast to this type of inheritance, with autosomal dominant diseases, the child can inherit the disease even from one of the parents.

The human body is made up of trillions of cells. Inside every cell there is a nucleus that contains our genetic material - chromosomes. Each person has 23 pairs of chromosomes - 46 chromosomes in total. We inherit this material from both of our parents. Chromosomes contain DNA that encode all of our metabolic processes, appearance, height, eye and hair color, intelligence, and other features. Defects in DNA, called mutations, can lead to disease, and they are "memorized" at the molecular level and passed on to new generations - this is the nature of genetic diseases.

There are two main types of mutations associated with hereditary hemochromatosis - C282Y and H63D. Numbers 282 and 63 indicate the location of defects in the HFE gene, which is located on the 6th chromosome.

People who inherit two C282Y mutations from each parent have a very high chance of developing hemochromatosis. In fact, such people make up 95% of all patients with hereditary hemochromatosis. Patients who inherited one C282Y mutation from one parent and one H63D mutation from the other parent account for another 3% of patients with hemochromatosis.

Symptoms of hereditary hemochromatosis

At an early stage of the disease, patients have no symptoms that allow one to suspect hemochromatosis and undergo a DNA test. Later, a high level of serum iron in the blood can be detected, which is detected by chance, during tests for another reason.

In men, symptoms of hemochromatosis may not appear until 40-50 years of age. In women, the first symptoms may appear 10, or even 15-20 years later than in men.

Iron deposits in the skin cause darkening of the skin, which is sometimes simply overlooked. Iron deposits in the pituitary gland and testes cause the testes to dry out and impotence. Iron in the pancreas causes decreased insulin production and diabetes. Deposits in the heart muscle lead to heart failure and arrhythmias. Liver damage causes scarring (cirrhosis) and an increased risk of liver cancer. Iron in the joints causes pain during movement and restriction of movement.

Diagnostics of the hemochromatosis

As already mentioned, in most patients, a suspicious increase in the level of iron in the blood is detected by chance. In some patients, at first, an increased level of liver enzymes is detected, which later leads to the diagnosis of hemochromatosis. It is much easier when patients know about hemochromatosis in their parents, so they come for an examination on this matter themselves.

Blood tests.

There are several blood tests that measure iron levels in the body: ferritin levels, serum iron levels, maximum iron binding capacity (TIBC), and transferrin saturation.

Ferritin is a blood protein that correlates with the amount of iron stored in the body. Ferritin levels are usually low in patients with iron deficiency anemia (IDA), but elevated in patients with hemochromatosis. Ferritin levels also increase with some infections (viral hepatitis) and other inflammatory processes, so this indicator alone is not enough for an accurate diagnosis.

Serum iron and transferrin saturation tests are done simultaneously. Serum iron reflects the amount of iron in the liquid portion (serum) of the blood. Binding capacity indicates the total amount of iron that can bind serum transferrin, a protein that carries iron molecules to different parts of the body.

Transferrin saturation is the number obtained by dividing the serum iron content by the maximum iron-binding capacity of the blood. This indicator indicates what percentage of transferrin is involved in iron transport. In a healthy person, transferrin saturation is in the range of 20-50%. In patients with IDA, this indicator is abnormally low, and in hereditary hemochromatosis it is very high (that is, most of the transferrin is "busy" with the transport of iron stores).

Serum iron levels may rise during the day, usually after meals. Therefore, blood tests should be done in the morning on an empty stomach.

Liver biopsy.

The most accurate test for hemochromatosis is to measure the iron content of the liver tissue. For this test, it is necessary to conduct a biopsy - take a small fragment of the patient's liver. Usually this procedure is done using a special long needle. The patient is anesthetized, and then a needle is inserted through the skin into the liver, and this procedure is controlled using an ultrasound machine. The tissue obtained from the biopsy is examined in the laboratory for signs of liver inflammation, cirrhosis (irreversible scarring), and the iron content is checked.

Liver biopsy in hemochromatosis also has prognostic value, since it determines the degree of irreversible scarring of the liver. Patients with hemochromatosis with relatively good biopsy results have a normal life expectancy (provided adequate treatment). Patients in whom hemochromatosis has already caused cirrhosis of the liver live much shorter lives.

Moreover, patients with cirrhosis have a dramatic increase in the risk of liver cancer (hepatocellular carcinoma), which can kill a person much earlier than cirrhosis would. When the liver is already affected, this risk remains high, even if hemochromatosis is actively treated.

Genetic analyzes.

The gene responsible for hereditary hemochromatosis was discovered back in 1996. This gene received the abbreviation HFE. Hereditary hemochromatosis in most patients is associated with C282Y and H63D mutations in this gene.

Most often (95%) patients with hemochromatosis have two C282Y mutations inherited from both parents. At the same time, not all people with such genetics suffer from the accumulation of iron in the body. Studies have shown that only 50% of people with the double C282Y mutation have hemochromatosis and its complications. That is, a positive genetic test is not a verdict yet.

The combined C282Y / H63D mutation occurs in children who inherited the C282Y mutation from one parent and H63D from the other parent. Most of these people have normal iron levels, but some have mild to moderate iron overload.

If a child inherits only one C282Y defect from one of the parents and the other HFE gene is normal, then he will not develop symptoms of iron overload. But such a person becomes a carrier of the disease. If both parents have such a defect, then each of their children will have a 25% chance of developing hemochromatosis.

1. Adults with suspected hereditary hemochromatosis (for example, close relatives of patients) should undergo blood tests for serum iron, ferritin, TIBC and transferrin saturation.
2. Patients with elevated serum iron, ferritin and transferrin saturation above 45% should undergo genetic testing.
3. Patients with a double mutation C282Y and transferrin saturation above 45% are considered to be patients with hemochromatosis. They must be treated (therapeutic phlebotomy).

Indications for liver biopsy.

Not all patients with hemochromatosis need liver biopsy. The goal of a liver biopsy is to identify patients with cirrhosis and to rule out other liver diseases (patients with cirrhosis often have liver cancer).

Young people under 40, carriers of two C282Y mutations, with normal liver enzymes and a serum ferritin level of less than 1000 ng / ml, have a very low risk of cirrhosis. In view of this, American experts recommend treating them with therapeutic phlebotomy without liver biopsy. These patients have an excellent prognosis with adequate treatment.

Patients over 40 years of age with elevated liver enzymes and serum ferritin levels of more than 1000 ng / ml have a serious risk of liver cirrhosis. The doctor may recommend a liver biopsy if the procedure is safe for the patient. The prognosis depends on the results of the biopsy.

Treatment of hereditary hemochromatosis

The most effective treatment for hemochromatosis is phlebotomy (phlebotomy) - the regular removal of some of the blood from the veins in the arms. For treatment, it is usually sufficient to take one unit of blood, or 450-500 ml, every 7-14 days (one unit of blood contains about 250 mg of iron).

It is recommended that serum ferritin levels and transferrin saturation be checked every 2-3 months. As soon as the ferritin level falls below 50 ng / ml with transferrin saturation below 50%, the phlebotomy frequency is reduced to 1 procedure every 2-3 months.

Benefits of therapeutic phlebotomy for hemochromatosis:

1. Prevention of cirrhosis and liver cancer if treatment is started early.
2. Improvement of liver function, in part also in patients with cirrhosis.
3. Overcoming symptoms such as weakness, fatigue, joint pain.
4. Improvement of heart function in patients with minor myocardial damage.

If hemochromatosis is diagnosed on time and intensively treated, then damage to the liver, heart, pancreas, testicles and joints can be completely avoided, and patients remain practically healthy people. In patients with pre-existing cirrhosis, organ function can be improved, but the scarring of the liver is irreversible and the risk of cancer remains high.

Dietary recommendations for patients with hereditary hemochromatosis:

1. A normal, balanced diet is permitted for all patients undergoing therapeutic phlebotomy. It is not necessary to avoid foods containing iron.
2. Avoid alcoholic beverages, because regular alcohol consumption negatively affects the liver, increases the risk of cirrhosis and hepatocellular carcinoma.
3. Taking large doses of vitamin C (ascorbic acid) in patients with iron overload can lead to fatal arrhythmias. Vitamin C supplements should be avoided until the disease is under control.
4. Do not eat raw sea food, as you can get dangerous infections that thrive in an iron-rich environment.

Early diagnosis of liver cancer in patients with hemochromatosis.

Liver cancer (hepatoma or hepatocellular carcinoma) occurs primarily in patients with liver cirrhosis. Thus, patients with hemochromatosis and cirrhosis should have regular ultrasound examinations (ultrasound) and blood tests for alpha-fetoprotein (a protein produced by the tumor). These tests should be done every six months.