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 / Causes of 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 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 sections 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, which is increased in diseases associated with excess iron accumulation.

With hemochromatosis, iron absorption 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 lipid, protein and DNA macromolecules.

An 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.
• Iron deposition 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, that is, 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 heterozygous carriage of the PHC allele. In such individuals, indirect signs may be found, indicating 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 iron in the blood serum is detected, but there is no life-threatening microelement 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 individuals 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. Most of the HFE protein is produced in the deep crypts of the duodenum. Normally, the role of the HFE protein in cryptonic 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, resulting in increased iron uptake. The main link in pathogenesis is a genetic defect in the 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 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 suffer from other diseases accompanied by disorders of iron metabolism.

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

Symptoms of Hemochromatosis:

Features: 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. Pain in the right hypochondrium, joints due to chondrocalcinosis of large joints, dryness and atrophic changes in the skin and testicles is often noted.

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 most frequent 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, hands), 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 it is painful on 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) gonads. Different kinds endocrinopathies occur in more than 80% of patients. The most frequent form 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 porphyria cutaneous tarda is possible.

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

The latent stage of PHC is observed in 30-40% of patients, which is revealed during the family genetic examination of the 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. Physical 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, the 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. 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 0.5 g of desferal, the excretion 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 was 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 signal intensity reduction is proportional to 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 biopsy specimens 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 functional tests the liver practically does not change, and according to the data of 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 of the bile ducts.

Histological examination in the terminal stage of the disease reveals a picture of generalized hemosiderosis with lesions of 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 causes of 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 from blood pathology (thalassemia, sideroblastic anemia, hereditary atransferrynemia, microcytic anemia, late cutaneous porphyria), liver diseases (alcoholic liver damage, chronic viral hepatitis, non-alcoholic steatohepatitis).

Treatment of Hemochromatosis:

Features of the treatment of hemochromatosis:

Shown is a diet rich in protein, no foods containing iron.

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 bloodletings 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 hemoglobin of erythrocytes. 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 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 can 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 often 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.

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 following a diet after it? Or do you need an inspection? You can make an appointment with the doctor - clinic Eurolab always at your service! Top Doctors will examine you, study external signs and help identify the disease by symptoms, advise you and provide help needed and diagnose. you also can call a doctor at home... Clinic Eurolab open for you around the clock.

How to contact the clinic:
The phone number of our clinic in Kiev: (+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 for a consultation with your doctor. If the research has not been performed, we will do everything necessary in our clinic or with our colleagues in other clinics.

You? You need to be very careful about your health in general. 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, in order not only to prevent a terrible disease, but also to maintain healthy mind in the body and the body as a whole.

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

Other diseases from the group Diseases of the gastrointestinal tract:

Grinding (abrasion) of teeth

Abdominal trauma

Abdominal surgical infection

Oral abscess

Adentia

Alcoholic liver disease

Alcoholic cirrhosis of the liver

Alveolitis

Angina Jensul - Ludwig

Anesthetic management and intensive care

Ankylosis of teeth

Dental anomalies

Tooth position anomalies

Developmental anomalies of the esophagus

Tooth size and shape abnormalities

Atresia

Autoimmune hepatitis

Achalasia cardia

Achalasia of the esophagus

Bezoars of the stomach

Disease and Budd-Chiari Syndrome

Veno-occlusive liver disease

Viral hepatitis in patients with chronic renal failure on chronic hemodialysis

Viral hepatitis G

Viral hepatitis TTV

Intraoral submucosal fibrosis (submucosal fibrosis of the oral cavity)

Hairy leukoplakia

Gastroduodenal bleeding

Geographic language

Hepatolenticular degeneration (Westphal-Wilson-Konovalov disease)

Hepatolienal syndrome (hepato-splenic syndrome)

Hepatorenal syndrome (functional renal failure)

Hepatocellular carcinoma (HCC)

Gingivitis

Hypersplenism

Gingival hypertrophy (gingival fibromatosis)

Hypercementosis (ossifying periodontitis)

Pharyngeal-esophageal diverticula

Hernia of the esophageal opening of the diaphragm (PAD)

Acquired esophageal diverticulum

Diverticula of the stomach

Diverticula of the lower third of the esophagus

Diverticula of the esophagus

Diverticula of the esophagus

Diverticula of the middle third of the esophagus

Dyskinesia of the esophagus

Dyskinesia (dysfunction) of the biliary tract

Liver dystrophies

Sphincter of Oddi dysfunction (postcholecystectomy syndrome)

Benign non-epithelial tumors

Benign neoplasms of the gallbladder

Benign liver tumors

Benign tumors of the esophagus

Benign epithelial tumors

Cholelithiasis

Fatty hepatosis (steatosis) of the liver

Malignant neoplasms of the gallbladder

Malignant tumors of the bile ducts

Foreign bodies of the stomach

Candidal stomatitis (thrush)

Caries

Carcinoid

Cysts and aberrant tissues in the esophagus

Speckled teeth

Upper GI Bleeding

Xanthogranulomatous cholecystitis

Leukoplakia of the oral mucosa

Medicinal liver damage

Medicinal ulcers

Cystic fibrosis

Mucocele of the salivary gland

Malocclusion

Development and eruption of teeth

Teeth formation disorders

Hereditary coproporphyria

Hereditary violation of the structure of enamel and dentin (Stanton-Capdepon syndrome)

Non-alcoholic steatohepatitis

Liver necrosis

Pulp necrosis

Emergencies in gastroenterology

Esophageal obstruction

Osteogenesis imperfecta of teeth

Examination of patients in emergency surgery

Acute delta superinfection in hepatitis B virus carriers

Acute intestinal obstruction

Acute intermittent (intermittent) porphyria

Acute violation of mesenteric circulation

Acute gynecological diseases in the practice of a surgeon

Acute bleeding from the digestive tract

Acute esophagitis

Acute alcoholic hepatitis

Acute appendicitis

Acute apical periodontitis

Acute acalculous cholecystitis

Acute viral hepatitis A (AHVA)

Acute viral hepatitis B (AVHV)

Acute viral hepatitis B with delta agent

Acute viral hepatitis E (OVHE)

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

Failure 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 specific clinical picturecharacterized by pigmentation of the skin and internal organs. The disease refers to a semi-systematic disease of the genetic type caused by a mutation in the HFE gene. The disease is more often associated with a transmitted mutation in the HFE gene on chromosome 6, which is why 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, multiple organ failure develops. The disease is always accompanied by cirrhosis, diabetes mellitus and dermal pigmentation.

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 hemochromatous gene is responsible for the appearance of the disease, which is present in the DNA of 5% of people on Earth, but the disease develops only in 0.3% of the population. The prevalence among men is 10 times higher than among women. In 70% of patients, the first symptoms appear at the age of 40-60.

Forms and stages of hemochromatosis

According to etiological factors, there are:

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

Hemochromatosis can be congenital or occur during life.

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 appears due to the defeat of another serious disease. Acquired enzyme deficiency, which accelerates the accumulation of iron, is:

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

Only the third degree of hemochromatosis has characteristic symptoms.

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

• I - light, no load, that is, iron metabolism is impaired, but its concentration does not exceed the norm;
• II - moderately severe, 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 idiopathic hemochromatosis. An ailment develops due to the degeneration of a gene that corrects metabolic processes with the participation of iron. A disease such as a mutation in the HFE gene is inherited.
2. Other pathologies, such as cirrhosis, hepatitis B and C untreated for more than six months, malignant tumors in the liver tissues or the hematopoietic system.
3. Vascular operations associated with portocaval bypass in the portal vein.
4. Accumulation of fat in the parenchyma of the "filter" not associated with alcohol intoxication.
5. Blockage of the main channel of the pancreas.
6. The introduction of specific intravenous drugs that provoke an increase in the concentration of iron.
7. Transfusion. Erythrocytes alien to the body are destroyed faster than their own. As a result of their death, iron is formed.
8. Continuous 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 hemochromatous change, an excessive accumulation of iron occurs in the tissues of organs, which begins to gradually destroy them. The inflammatory process begins at the site of the lesion. Local immunity in order to suppress the focus activates the process of fibrin scarring. As a result, fibrosis of the affected organ develops and its failure. 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. Development of general weakness and malaise is possible. As the disease progresses, symptoms of disruption of the work of other organs appear, expressed:

Hemochromatosis provokes pigmentation, abdominal pain, gastrointestinal disorders, headaches.

• pigmentation of the dermis in the face, 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 face and body;
• non-localized abdominal pain of varying strength;
• gastrointestinal disturbances, including nausea with vomiting, diarrhea, lack of appetite;
• dizziness;
• limitation of the motor ability of the joints due to damage and deformation.

The most common symptom complex in hemochromatous changes are symptoms of cirrhosis of the parenchyma, diabetes mellitus against the background of severe pigmentation of the dermis. Symptoms appear when the iron level exceeds 20 g, which is 5 times 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. Hepatic dysfunction when basic functions are not performed.
2. Any heart rhythm disturbances 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, more often in the hepatic tissues.
8. Diabetes mellitus, which develops in 75% of cases.
9. Hepatomegaly, when the liver enlarges.
10. Splenomegaly is an increase in the volume of the spleen.
11. Diffuse progressive cirrhosis of the parenchyma.
12. Arthralgia, when the joints are very painful. The interphalangeal joints on the second and third fingers are especially affected.
13. Sexual disturbances such as impotence (in men). In women, amenorrhea develops, as a result, a decrease in libido.
14. Damage to the pituitary gland and associated hormonal deficiency.

Diagnostics

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

The final diagnosis of a malfunction in iron metabolism can only be made after a comprehensive examination by a dermatologist, urologist, cardiologist and other specialists.

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

But all doctors will use a unified approach in diagnosing a 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 the damage to the body.

Diagnostics is aimed at identifying the disease itself by specific methods, since the standard list of analyzes is uninformative. Today it is proposed step by step diagram diagnosing a pathological condition, 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 the substance in women during the period outside and after menopause is 200 and 300 units, respectively.
3. Diagnostic bloodletting. The essence of the method is to extract a small amount of blood with the calculation of iron in the serum. Usually, the patient gets better when the iron level in the general bloodstream drops by 3 grams.

Laboratory methods

Hemochromatosis is also diagnosed based on the results of blood and urine tests.

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 diagnostic methods are used as:

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

To confirm the diagnosis, a puncture or dermis is performed with subsequent examination for the presence / absence of hemosiderin deposits. The hereditary form of the disease is determined on the basis of data obtained during molecular genetic research.

To assess the severity of damage to other organs and determine the prognosis:

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

Instrumental techniques

In addition to clinical research of the patient's biological fluids, an instrumental examination is carried out, which allows you to get a more accurate picture of the flow, the prevalence of the pathological process, and determine the damage to the body. To do this, appoint:

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

The general definition of diseases associated with increased accumulation of iron in the liver includes the following criteria: 1) cirrhosis and liver fibrosis with an initial predominant accumulation

iron in parenchymal cells, as well as with its presence in stellate reticuloendotheliocytes; 2) iron deposition in other organs, including the pancreas, heart, pituitary gland; 3) increased absorption of iron, which leads to its adsorption and accumulation.

The clinical concept of siderosis (iron storage disease) includes idiopathic (hereditary) hemochromatosis and hemochromatosis syndrome due to the influence of various etiological factors: anemia, alcoholic cirrhosis, increased intake of iron into the body, as well as hemosiderosis with massive transfusions, chronic hemodialysis,

A number of researchers attribute to this group such early stages of the disease, when there is iron deposition in the parenchymal cells of the liver, but there are no signs of cirrhosis and fibrosis, especially if these patients belong to families with hereditary disorders of iron metabolism. Isolation and treatment of patients at this stage can be critical in preventing complications of hemochromatosis. There is strong evidence that iron deposition in hepatocytes is toxic, while increased iron deposition in mature reticuloendotheliocytes is quite benign.

Despite the fact that there are some deviations from the above definition, the classification of sideroses, based on the principle of the predominant accumulation of iron in parenchymal or mature reticuloendothelial cells, is generally accepted.

The term hemosiderosis is used to describe conditions with a predominant accumulation of iron in the cells of the reticuloendothelial system (the system of phagocytic macrophages). Hemosiderosis occurs without documented cases of cirrhosis; in the future, we will consider only disorders with a predominant deposition of iron in parenchymal cells - hemochromatosis.

Hemochromatosis differs from hemosiderosis in that, firstly, iron-containing pigment accumulates mainly in parenchymal cells, and secondly, the accumulation of pigment leads to damage to tissues and organs.

From a clinical point of view, it seems to us the most important to emphasize the need to isolate idiopathic hemochromatosis as an independent nosological unit and hemochromatosis as a syndrome of iron accumulation in a number of diseases.

The main indicators of iron metabolism. The iron content in the adult human body is 4-5 g, more than half of this amount is in hemoglobin and 15% in skeletal muscles as iron not included in heme; 35% of iron is deposited in the liver, spleen, bone marrow. The liver is the main organ - a depot, containing up to 500 mg of iron in the norm. Various enzymes (catalase, cytochromes) contain a minimum amount of iron.

The iron depositing protein is ferritin, the transporting protein is transferrin. During normal metabolism, iron deposited in hepatocytes in the form of ferritin is not detected in the Perls reaction.

A healthy person loses about 1 mg of iron per day, and women during menstruation - another 15-20 mg per month. The greatest losses of iron (about 70%) occur through the gastrointestinal tract, the rest of the iron is lost in the urine and through the skin. A normal diet contains 10-11 mg of iron, of which only 1-2 mg is absorbed; at iron deficiency anemia iron absorption rises to 3 mg / day. Patients with hemochromatosis continue to absorb increased amounts of iron. Excessive deposition of iron in tissues, primarily in parenchymal and stellate reticuloendo-teliocytes of the liver, occurs in the form of a pigment hemosiderin. Hemosiderin is a brownish-yellowish pigment with a granular structure; it is not normally detected in the liver tissue. On microscopic examination, hemosiderin is detected by the Perls reaction in the hepatocytes of the periportal zones of the hepatic lobules. The place of intracellular localization of hemosiderin is lysosomes. All liver damage caused by high iron levels is collectively referred to as siderosis.

10.2.1. Idiopathic (hereditary) hemochromatosis

Idiopathic hemochromatosis (siderophilia, primary hemochromatosis, hereditary disease accumulation of iron), the former names of the disease - bronze diabetes, pigmentary cirrhosis.

Idiopathic hemochromatosis is a hereditary metabolic disease with high absorption of iron in the intestine and its primary deposition in hepatocytes. Increased deposition of iron in hepatocytes leads to fibrosis, disruption of liver architectonics up to cirrhosis. In other organs, especially endocrine glands, heart, skin, mucous membranes, pancreas, morphological and functional changes associated with iron deposition are also found.

The main link in pathogenesis is, apparently, a genetic defect in the enzyme systems that regulate the absorption of iron in the intestine during normal intake of it with food.

The disease is transmitted in an autosomal recessive manner. A clear connection has been established between idiopathic hemochromatosis, a congenital enzymatic defect leading to the accumulation of iron in the internal organs, and the histocompatibility antigens HLA, especially A3, B14, in the UK and Australia - also with HLA-B7. The fact that the proband has two HLA haplotypes indicates high degree risk in siblings, but not in offspring. To more accurately determine the risk in relatives, it is important to simultaneously examine the level of serum ferritin and histocompatibility antigens. The gene that controls the iron content in the body

nizme, located on the 6th chromosome. Genotypic study of a number of histocompatibility antigens of the HLA system, controlled by the 6th pair of chromosomes, fully confirmed the recessive mode of inheritance.

Frequency. In the UK and Scandinavian countries, idiopathic hemochromatosis is detected very rarely, in the countries of Central Europe - much more often and amounts to 0.01-0.07%. In the United States, the frequency ranges from 0.001 to 0.1% of the general population.

Men get sick about 10 times more often than women, usually between the ages of 40-60, women - in most cases after menopause,

Morphological changes. The skin and internal organs are rusty-brown or chocolate brown. The liver is especially highly pigmented. In light-optical examination, hepatocytes, especially perigurtal ones, are overfilled with hemosiderin, which gives a positive Psrls reaction to iron. Hemosiderin is also detected in stellate reticuloendotliocytes, but in much smaller amounts than in hepatocytes.

The activity of redox enzymes is found mainly in young, pigment-free regenerating cells. In cells loaded with pigments, their activity is weak or absent (Fig. 30). Gradually, the amount of pigment in hepatocytes increases, their necrosis occurs, fibrosis of the liver tissue joins. Hemosiderin appears in the epithelial cells of the bile ducts and tubules, in connective tissue.

Fibrous layers dissect the parenchyma into small fragments, in some places false lobules are visible. At the end of the process, a picture of predominantly micronodular cirrhosis develops, which can turn into macronodular. Characteristic feature cirrhosis in hemochromatosis are wide septa of mature connective tissue surrounding the false lobules.

The pancreas is especially affected by hemochromatosis. In addition to significant deposits of pigment, interstitial inflammation and fibrous changes are found in it, and atrophy of the Langerhans islets occurs. Changes in the spleen are similar to those found in other forms of cirrhosis.

Pigment deposition is observed in the spleen, myocardium, pituitary gland, adrenal glands, thyroid gland, parathyroid glands, ovaries, synovial tissue of the joints, skin. In the skin, the pigment is detected in cutaneous macrophages, fibroblasts, the amount of melanin increases.

The clinical picture.The onset of the disease is gradual; characteristic symptoms appear only after 1-3 years. In the initial stage, for a number of years, complaints of pronounced weakness, fatigue, weight loss, and decreased sexual function in men predominate. Pain in the right hypochondrium, joints in connection with chondrocalcinosis of large joints, dryness and atrophic changes in the skin, testicular atrophy are often noted.

In the advanced stage of the disease, hemochromatosis is manifested by the classic triad: pigmentation of the skin and mucous membranes, liver cirrhosis and diabetes.

Pigmentation of the skin and mucous membranes is one of the most frequent and early symptoms of hemochromatosis; according to different authors, it occurs in 52-94% of patients. The severity of pigmentation depends on the duration of the disease. Bronze or smoky skin color is more noticeable on open parts of the body (face, neck, hands), on previously pigmented areas, in the armpits, on the genitals.

Primary hemochromatosis is a disease that is positioned as hereditary, that is, one that was caused by a chromosomal or gene mutation. Such a disease differs from others at least in that, if it occurs and develops, physicians have the opportunity to establish the exact cause that provoked it, since it is associated with damage to the hereditary apparatus.

Primary hemochromatosis - as mentioned above, a genetically determined disease, as a result of the development of which there are disturbances in the metabolic mechanism, namely, iron. Excessive amounts of iron accumulate in tissues and organs. Iron, which enters the body with food, as a result of excessive activation of the process of its absorption in the gastrointestinal tract, begins to be deposited in tissues and organs: pancreas, liver, spleen, myocardium, skin, endocrine glands, heart, pituitary gland, joints and others.

Primary hemochromatosis got its name at the end of the nineteenth century, as a reflection of one of its most pronounced symptoms - pigmentation skin and organs. Also, synonyms to its name are based on this symptom of the disease - bronze diabetes, pigmentary cirrhosis. Interestingly, primary hemochromatosis was first described by physicians as a complex of symptoms, the characteristic signs of which are diabetes mellitus, cirrhosis of the liver, pigmentation of the skin and mucous membranes, provoked by the accumulation of the trace element iron in tissues and organs.

In our time, due to the improvement of diagnostic methods, there is an increase in hemochromatosis disease. With the advent of population genetic studies, the reputation of primary hemochromatosis as a rare disease has disappeared. Such studies show that the likelihood of developing primary hemochromatosis hovers around the figure of 0.33 percent. The World Health Organization reports that ten percent of the population is prone to developing primary hemochromatosis. It is also noted that men are exposed to primary hemochromatosis about ten times more often than women.

Causes of occurrence

Often, the onset and development of primary hemochromatosis is triggered by a mutation in the HFE gene. Primary hemochromatosis, which is not related to the HFE gene mutation, is considered a rare occurrence and is associated with the presence of ferrosportive disease, hemochromatosis of the juvenile and rare neonatal type, hypostransferrinemia and uceroloplasminemia. According to research statistics, eighty percent of cases of hemochromatosis caused by the HFE gene are homozygous mutation C282Y and heterozygous mutation of the combined type - C282Y / H63D. Primary hemochromatosis is an autosomal recessive disorder, which means that both the mother and the father are carriers of the defective gene.

Pathophysiology of primary hemochromtosis

A healthy person has about four grams of iron in the body. This amount of iron is found in hemoglobin, catalase, myoglobin and other enzymes and pigments of the respiratory system. The occurrence of a pathological process should be discussed when the excessive iron content reaches twenty grams. Over time, the mass of excess iron in primary hemochromatosis can be up to sixty grams.

Symptoms of primary hemochromatosis

The symptomatology of hemochromatosis acquires a pronounced character when the concentration of iron in tissues and organs reaches a total amount of twenty to forty grams, that is, already in a solid mature: at forty to sixty years for men, and even later - for women. The development of pathology occurs in stages:

• First stage. At this stage, the patient's body is still overloaded with iron by genetic tendency.
• Second stage. In the second stage, the iron-overloaded body still does not show clinical signs.
• Stage Three. At this, last, stage, the patient has clinical manifestations.

Hemochromatosis is gradual. In an early stage of development, patients may experience remarkable fatigue and weakness for years, observe weight loss, and men - sexual dysfunction. Also at this stage of the disease, excruciating pains in the joints and the right hypochondrium may occur, the skin undergoes atrophic changes and dryness, and in men, the testicles. The developed hemochromatosis has symptoms, classic for physicians, consisting of three components - pigmentation of the mucous membranes and skin, diabetes and cirrhosis of the liver.

Pigmentation. In cases of diagnosing hemozramatosis, according to medical statisticians, pigmentation is the first and most common symptom. The severity of pigmentation depends on how long the disease has already developed. In places that already had experience of pigmentation - hands, face and neck, the skin acquires a more pronounced smoky-bronze tint, and pigmentation in hemochromatosis affects the genitals and armpits.

In most cases, doctors diagnose excess iron deposition in the liver. At the same time, there is an increase in its size, tissue compaction, the surface becomes smooth. Pain on palpation is possible.

Often, the development of hemochromotosis is accompanied by pathologies of the endocrine system (hyperfunction of the adrenal glands, pituitary gland, thyroid gland, pineal gland and gonads).

Treatment of the disease

The mainstay of treatment for hemochromatosis is the removal of excess iron from the patient's body. Further, doctors are making every effort to possibly restore or maintain the normal functioning of organs that have been affected by the disease.

To remove excess iron, doctors resort to using the bloodletting procedure, which is considered the simplest for this purpose. This procedure is also called phlebotomy and venesection. It consists in temporarily cutting the surface of the vein to release two hundred to five hundred milliliters of blood. Bloodletting is carried out once or twice a week for several years (two to three years) until the moment when the patient's blood iron level is normalized. Thanks to the bloodletting procedure, excess iron is removed from the body, the degree of skin pigmentation and the size of the liver decreases, and the patient's overall well-being improves.

An alternative or additional means to bloodletting can be iron-binding drugs - a group of medications that chemically bind to iron and remove it from the body.

Diet is the second most important component of liver hemochromatosis treatment. The patient needs to reduce his food products, which contain iron and protein (meat, apples, buckwheat, pomegranate), also reduce the amount of ascorbic acid entering the body, since it increases the degree of absorption of iron into the body, and absolutely refuse to drink alcohol which impairs liver function.

Prevention of hemochromatosis

When diagnosing hemochromatosis, in order to prevent further complications, the patient must follow a diet that restricts food intake with iron, ascorbic acid, vitamin C, and foods with a large amount of protein. Prevention of hemochromatosis also includes taking iron-binding medications, but only under strict medical supervision. To prevent hemochromatosis, your doctor may prescribe a metered dose of iron medications.

If you still have questions about primary hemochromatosis, then ask them right now on this site!

Hemochromatosis was first described as a separate disease in 1889. However, it was possible to accurately establish the causes of the disease only with the development of medical genetics.

This rather late classification was facilitated by the nature of the disease and its rather limited spread.

So, according to modern data, 0.33% of the world's inhabitants are exposed to the threat of hemochromatosis. What is the cause of the disease and what are its symptoms?

What is hemochromatosis?

This disease is hereditary and is characterized by a multiplicity of symptoms and a high risk of serious complications and comorbidities.

Studies have shown that hemochromatosis is most often caused by a mutation in the HFE gene.

As a result of a gene failure, the mechanism of iron capture in the duodenum is disrupted... This leads to the fact that the body receives a false message about the lack of iron in the body and begins to actively and in excess amounts to synthesize a special protein that binds iron.

This leads to excessive deposition of hemosiderin (glandular pigment) in the internal organs. Simultaneously with an increase in protein synthesis, the gastrointestinal tract is activated, leading to excessive absorption of iron from food in the intestine.

So even with a normal diet, the amount of iron contained in the body is many times higher than the norm. This leads to the destruction of tissues of internal organs, problems with the endocrine system, immunity.

Classification by types, forms and stages

In medical practice, primary and secondary types of the disease are distinguished. In this case, the primary, also called hereditary, is the result of manifestation. Secondary hemochromatosis is a consequence of the development of deviations in the work of enzyme systems involved in glandular metabolism.

There are four forms of hereditary (genetic) type of the disease:

• classical;
• juvenile;
• hereditary HFE-unassociated species;
• autosomal dominant.

The first type is associated with the classic recessive mutation of the sixth chromosome region. This type is diagnosed in the vast majority of cases - more than 95 percent of patients suffer from just classic hemochromatosis.

The juvenile type of the disease occurs as a result of mutation of another gene - HAMP. Under the influence of this change, the synthesis of hepcidin, an enzyme responsible for the deposition of iron in organs, increases significantly. Usually the disease manifests itself between the ages of ten and thirty.

The HFE-unassociated type develops when the HJV gene fails. This pathology includes the mechanism of transferrin-2 receptor hyperactivation. As a result, the production of hepcidin is activated. The difference with the juvenile type of the disease is that in the first case, the gene that is directly responsible for the production of an iron-binding enzyme is disrupted.

Whereas in the second case, a state characteristic of an excess of iron in food is created in the body, which leads to the production of an enzyme.

The fourth type of hereditary hemochromatosis is associated with a malfunction of the SLC40A1 gene.

The disease manifests itself in old age and is associated with improper synthesis of the protein ferroportin, which is responsible for the transport of iron compounds into cells.

Missense mutation causes and risk factors

A genetic mutation in a hereditary type of disease is a consequence of a person's predisposition.

Studies show that the majority of patients are white in North America and Europe, with the largest number of hemochromatosis sufferers occurring among people from Ireland.

At the same time, the prevalence of different types of mutation is characteristic for different parts of the world. Men are susceptible to the disease several times more often than women. In the latter, symptoms usually develop after hormonal changes in the body, resulting from menopause.

Among the registered patients, women are 7-10 times less than men. The reasons for the changes are still unclear. Only the hereditary nature of the disease has been irrefutably proven, and there is also a connection between the presence of hemochromatosis and.

Despite the fact that the proliferation of connective tissue cannot be directly explained by the accumulation of iron in the body, up to 70% of patients with hemochromatosis had liver fibrosis.

In this case, a genetic predisposition does not necessarily lead to the development of the disease.

In addition, there is a secondary form of hemochromatosis that occurs in people with initially normal genetics. Some pathologies also belong to risk factors. So, transferred steatohepatitis (non-alcoholic adipose tissue), development chronic hepatitis different etiologies, as well as blockage contribute to the manifestation of the disease.

Some malignant neoplasms can also be a catalyst for the development of hemochromatosis.

Symptoms of hemochromatosis in women and men

In the past, only the development of a number of serious symptomatic manifestations allowed to diagnose this disease.

A patient with an excessive accumulation of iron feels chronic fatigue, weakness.

This symptom is typical for 75% of those suffering from hematochromatosis. Skin pigmentation is enhanced, and this process is not associated with the production of melanin. The skin acquires a dark shade due to the accumulation of iron compounds there. Darkening occurs in more than 70% of patients.

The negative effect of accumulated iron on immune cells leads to a weakening of the immune system. Therefore, with the course of the disease, the patient's susceptibility to infections increases - from rather serious to commonplace and harmless under normal conditions.

About half of patients suffer, which are expressed in the occurrence of pain syndrome.

There is also a deterioration in their mobility. This symptom occurs because an excess of iron compounds leads to the catalization of calcium deposition in the joints.

Arrhythmia attacks and the development of heart failure are also possible. A negative effect on the pancreas often leads to. Excess iron causes dysfunction of the sweat glands. In rare enough cases, they are observed.

The development of the disease leads to impotence in men. Decreased sexual function indicates signs of body poisoning with iron compounds. In women, profuse bleeding is possible during regulation.

An important symptom is an enlarged liver, as well as sufficiently severe abdominal pain, in the appearance of which it is not possible to identify systemic character.

The presence of several symptoms indicates the need for accurate laboratory diagnostics diseases.

A sign of the disease is high, with a simultaneous low content in erythrocytes. Iron transferrin saturation values \u200b\u200bbelow 50% are considered a laboratory sign of hemochromatosis.

The presence of complex heterozygotes or homozygous mutations of a certain type in the HFE gene with clinical evidence of excess iron accumulation indicates the development of hemochromatosis.

A significant increase in the liver with a high density of its tissues is also a sign of disease. In addition, with hemochromatosis, a change in the color of liver tissue is observed.

How does it manifest in a child?

Early hemochromatosis has a number of features - from the mutations that caused it in the corresponding sections of the chromosomes to the characteristic clinical picture and manifestations.

First of all, the symptoms of the disease at an early age are polymorphic.

For children, the development of symptoms is characteristic, indicating the presence of a portal... A violation of the assimilation of food develops, a simultaneous increase in the spleen and liver.

With the development of pathology, severe and resistant to therapeutic effects of ascites begins - dropsy, which forms in the abdominal region. The development of varicose veins of the esophagus is characteristic.

The course of the disease is severe, and the prognosis of treatment is almost always unfavorable. In almost all cases, the disease provokes a severe form of liver failure.

What analyzes and diagnostic methods help to identify pathology?

Several different laboratory methods diagnostics.

Initially, blood samples are taken to study the level of hemoglobin in erythrocytes and plasma.

Iron metabolism is also assessed.

The desferal test helps to confirm the diagnosis. For this, an injection of a glandular preparation is injected, and after five hours a urine sample is taken. Additionally, CT scan is performed, as well as MRI of internal organs, which allows to determine their pathological changes - an increase in size, pigmentation, changes in tissue structure.

Molecular genetic scanning allows you to determine the presence of a damaged chromosome section. This studycarried out with family members of the patient, also allows us to assess the possibility of the onset of the disease even before the appearance of its clinical manifestations that disturb the patient.

Treatment principles

The main methods of treatment are the normalization of the iron content in the body and prevention of damage to internal organs and systems. Unfortunately, modern medicine does not know methods of normalizing the gene apparatus.

Bloodletting

Bloodletting is a common treatment. At initial therapy, 500 mg of blood is removed weekly. After normalization of the iron content, they switch to maintenance therapy, when blood is taken every three months.

Intravenous administration of iron-binding drugs is also practiced. So, chelators allow you to remove excess substances in the urine or feces. However, the short period of action necessitates regular subcutaneous injection of medications using special pumps.

Laboratory control is carried out once every three months. It includes calculating the iron content, as well as diagnosing signs of anemia and other consequences of the disease.

Possible complications and prognosis

With early diagnosis, the disease can be effectively controlled.

The duration and quality of life of patients who receive regular care practically do not differ from those of healthy people.

At the same time, untimely treatment leads to serious complications. These include the development of cirrhosis and liver failure, diabetes, venous damage up to bleeding.

The risk of developing cardiomyopathy and liver cancer is high, and intercurrent infections are also observed.

Related Videos

About what hemochromatosis is and how to treat it: