Hereditary sideroblastic anemia - options, diagnosis, treatment. Sideroblastic anemia

Sideroblastic anemia is characterized by reduced level iron in red blood cells due to its non-use by the bone marrow for the synthesis of hemoglobin. Gradually, the level of iron increases not only in the blood, but also in the internal organs.

Causes and symptoms of types of pathology

Anemia is pathological condition, in which the amount of hemoglobin in the blood decreases. Sideroblastic anemia can develop as a result of:

• hereditary factor;
• various neoplasms (multiple myeloma, leukemia);
• poisoning with chemical microelements (lead, zinc);
• pathology, the cause of which was own immunity(rheumatoid arthritis);
• taking tuberculostatic drugs (isoniazid);
• alcohol intoxication;
• age (over 50 years).

Patients are concerned about:

• weakness;
• fast fatiguability;
• hair loss;
• headache;
• increased brittleness of nails;
• pain in the heart area of ​​a compressive nature;
• shortness of breath after exercise.

Sometimes this type of anemia is accompanied by jaundice skin, enlarged spleen and liver.

Signs of pathology can be different and depend on the age of the patient and the type of disease. The severity of manifestations ranges from mild ( clinical symptoms minor) to severe (requires regular red blood cell or blood transfusions).

Hereditary

The disease occurs more often in boys and is found in childhood. The pathology is caused by genetic changes. Among hereditary anemias there are:

• Pearson syndrome;
• linked to the X chromosome;
• mitochondrial with anemia syndrome;
• erythropoietic porphyria.

Hereditary sideroblastic anemia is characterized by the following manifestations:

• headache;
• weakness;
• inattention;
• fatigue;
• deterioration of memory and academic performance.

On external examination, the skin is pale, the spleen and liver are enlarged.

Congenital

The congenital form of the disease can lead to the accumulation of iron in tissues and the development of hemosiderosis, accompanied by:

• signs of diabetes;
• liver dysfunction;
• pathologies of the heart;
• pulmonary insufficiency;
• “bronze” pigmentation of the skin.

Acquired

It is not always possible to detect the cause of acquired sideroblastic anemia. More often, pathology occurs in elderly patients. If a patient has anemia, but its etiology is unknown, it is considered to be an idiopathic form of the disease.

There are symptomatic sideroblastic anemias that develop as a result of:

• the influence of certain medicinal or toxic substances;
• lack of copper;
• chronic inflammatory processes;
• malignant neoplasms.

Signs of the disease:

• pale skin;
• enlarged liver and spleen (in 30% of cases);
• disturbances of heart rhythm and liver function.

In some cases (from 7 to 20%), the idiopathic form transforms into acute leukemia.

Treatment and prognosis

When prescribing treatment, the form of the disease is taken into account. An important role is given to a proper lifestyle and diet.

In the case of an acquired form of the disease (as far as possible), it is necessary to exclude factors that cause chronic intoxication. Patients are given vitamin B6 for 2 months. After 3 months, the level of hemoglobin in the blood returns to normal.

If the form of the pathology turns out to be resistant to pyridoxine (vitamin B6), anabolic agents are used, and Desferal is prescribed to remove excess iron.

In case of severe pathology, red blood cells are transfused. After this, hemosiderin deposition may begin. Deferoxamine is used to prevent hemosiderosis.

Rarely used surgery: To restore proper hemoglobin synthesis, resection of the spleen is performed (partial or complete). However, this method increases the risk of blood clots.

It is necessary to exclude foods containing zinc from the diet (it contributes to increased manifestations of the disease): nuts, liver, hard cheeses. It is necessary to stop drinking alcoholic beverages.

Once hemoglobin and iron levels are restored, treatment ends. The patient must visit the doctor and undergo tests within a year.

At congenital pathology and started in a timely manner proper treatment the prognosis is favorable. If the disease is detected late and treatment is not prescribed for a long time, irreversible phenomena develop in tissues and organs. In this case, the prognosis worsens.

Acquired sideroblastic anemia may resolve without treatment after eliminating the provoking factors. The idiopathic form can be severe if it transforms into acute leukemia.

In contact with

Hereditary sideroblastic- heterogeneous in the range of genetic disorders and severity clinical manifestations group of diseases.

Variants of inheritance and pathogenesis

X-linked hereditary sideroblastic anemias. In most children with sideroblastic anemia, the mechanism of inheritance is associated with the X chromosome. In this regard, anemia is diagnosed mainly in boys and their close male relatives on the maternal side (uncles and cousins). Rarely there is another mode of inheritance that is not associated with the X chromosome. In some families, the disease occurs only in girls, since in homozygous boys the pathology is not compatible with life.

The pathogenesis is based on a defect in synthesis 5-aminolevulinate synthetase(ALA), involved in heme synthesis. For normal operation This enzyme requires a sufficient amount of pyridoxine - vitamin B6 (this explains the effectiveness of treatment with vitamin B6). The activity of the enzyme 5-aminolevulinate synthetase (ALA synthetase) is encoded by the ALAS2 gene, located on the X chromosome. Several different mutations of this gene have been described in patients with sideroblastic anemia.

Hereditary sideroblastic anemias with autosomal inheritance. This type of inheritance is much less common than X-linked inheritance. There are cases of both autosomal dominant and autosomal recessive inheritance. Mutations of the ALAS2 gene are not detected, so there is no therapeutic effect of pyridoxine.

Sporadic congenital sideroblastic anemia. About 20 cases of sideroblastic anemia, detected immediately after birth, without signs of the disease in other family members, have been described in the world. Probably, there was either an autosomal recessive type of inheritance or the appearance of new mutations of the ALAS2 gene in the parental germ cells.

Mitochondrial cytopathy (Pearson syndrome). Pearson syndrome - congenital disease, which is caused by deletions or other genetic rearrangements of mitochondrial DNA and is clinically manifested by multiple organ lesions. One of early signs The disease is severe anemia associated with the presence of ring sideroblasts in the bone marrow. The life expectancy of children with Pearson syndrome usually does not exceed 2-3 years.

DIOMOAD syndrome. Most clinical manifestations of the disease, which is inherited in an autosomal recessive manner, are based on degenerative processes in the nervous tissue, probably caused by hereditary defects in thiamine metabolism. The hematological manifestation of the syndrome is normocytic sideroblastic anemia medium degree severity in combination with neutropenia and severe thrombocytopenia. The therapeutic effect of using thiamine has been noted.

Data from clinical and laboratory studies in hereditary sideroblastic anemia

In most cases, the clinical picture sideroblastic anemia, linked to the X chromosome, does not differ from that of anemia with autosomal inheritance or other congenital forms. Severe anemia is usually diagnosed in infancy or early childhood. With less pronounced manifestations of anemic syndrome or asymptomatic the disease is usually detected in adults or even elderly patients.

Along with with anemic syndrome All patients exhibit signs of excess iron in the body, which are given a special name: erythropoietic hemochromatosis syndrome. The manifestations of this syndrome are quite varied. Most often, moderate hepatomegaly and splenomegaly are detected. Liver function in most cases is slightly impaired or not affected at all. A liver tissue biopsy reveals iron deposits in hepatocytes. In some patients over 30-40 years of age, histological examination reveals signs of micronodular cirrhosis of the liver, which is usually benign.

On the background hemochromatosis pancreas can be determined diabetes or impaired glucose tolerance. Rarely, an objective examination reveals pigmentation of the skin. Most dangerous manifestations syndrome of erythropoietic hemochromatosis are severe disorders heart rate and heart failure, which usually develops later stages diseases. IN severe cases Children may experience delayed growth and development.

In analysis blood anemia is determined varying degrees gravity. In severe anemia, there is usually hypochromia, microcytosis, aniso- and poikilocytosis, less often target cells and single siderocytes. At less severe forms anemia, two cell populations can be detected in a smear: hypochromic microcytes and normal red blood cells. In this case, a two-phase curve is formed on the histogram of erythrocytes, reflecting differences in the sizes of erythrocytes. The level of white blood cells and platelets is usually normal, but may decrease with the development of hypersplenism. The reticulocyte count is normal or slightly increased in most cases.

IN myelogram hyperplasia of the erythroid germ is detected against the background of the normoblastic type of hematopoiesis and increased amount sideroblasts. IN in rare cases(with concomitant folic acid deficiency), the megaloblastic type of hematopoiesis can be determined.

With biochemical research Usually there is a slight hyperbilirubinemia, an increase in ferritin levels and a decrease in transferrin levels, and an increase in its saturation. In X-linked anemia, there is a decrease in ALA synthetase activity.

In patients with Pearson syndrome refractory sideroblastic anemia is diagnosed, which is combined with signs of exocrine pancreatic insufficiency, episodes of lactic acidosis and progressive renal and liver failure. Anemia is usually detected after birth and is normocytic or macrocytic in nature. The reticulocyte level is most often reduced. In most cases, there is neutropenia and thrombocytopenia of varying severity. Hemoglobin electrophoresis usually reveals an increase in the level of Hb F. The bone marrow is hypercellular or normocellular, ring sideroblasts are detected.

Treatment and prognosis of hereditary sideroblastic anemias

To all the sick hereditary sideroblastic anemias it is necessary to begin therapy with pyridoxine (vitamin B6), which is effective on average in 1/3 of cases. The dose of vitamin B6 is usually 50-100 mg per day. Expressiveness therapeutic effect in patients who respond to treatment varies. In most cases, reticulocytosis appears and the hemoglobin level gradually increases to normal or sub-normal over the course of 1-2 months of treatment. normal values. Morphological changes in erythrocytes are preserved.

With absence optimal effect During pyridoxine therapy, hemoglobin levels stabilize, but do not reach normal values. It is necessary to carry out maintenance therapy with vitamin B6, in the absence of which the hemoglobin concentration decreases to its original values ​​after a few months. If a megaloblastic type of hematopoiesis is detected, treatment is indicated folic acid. For patients with severe anemia who do not respond to vitamin B6, periodic transfusions of red blood cells are given as indicated. This reduces the severity of anemia and prevents growth and development delays in children.

For prevention hemosiderosis Deferoxamine therapy is indicated, which is needed primarily in patients with severe anemia receiving blood transfusion therapy. Preferably, 12-hour subcutaneous infusions of the drug at a dose of 40 mg/(kg-day) every 5 days of the week (this regimen has minimal toxicity). Splenectomy for hereditary forms of sideroblastic anemia is quite often complicated by thromboembolism, in some cases with fatal, That's why surgical treatment rarely used.

Sideroachrestic anemia does not have a pronounced clinical picture. May be present increased fatigue, weakness. Most often, patients consult a doctor general practice, which redirects to the reception that conducts:

During the examination, the specialist will find out from the patient:

1. general state;
2. Lifestyle;
3. Availability bad habits;
4. past illnesses;
5. presence of diseases in relatives.

For sideroachrestic anemia, a series of laboratory research. Among them:

• general blood analysis;
• blood chemistry;
• cell composition study bone marrow;
• liver biopsy.

The overall examination strategy may include radiological and endoscopic examinations, consultations with a gynecologist, proctologist, urologist, phthisiatrician. If there is a hereditary form of sideroblastic anemia, patients should definitely consult a geneticist.

Treatment methods for sideroachrestic anemia

A necessary step for the treatment of iron-refractory anemia is the establishment and subsequent elimination of immediate cause occurrence of the disease. It is necessary to exclude or limit the effect on the human body.

Many people know that anemia is quite dangerous disease. There are many varieties of this disease, and each of them is harmful to human health. Sideroblastic anemia is dangerous pathology associated with impaired synthesis of microelements. In this case, iron is used to combine hemoglobin, so it is deposited in the internal organs. The main thing is to prevent complications, and for this you need to promptly seek help from a specialist.

Concept

Sideroblastic anemia differs from other types of disease by a reduced concentration of iron in red blood cells. The fact is that the bone marrow does not use this element in the synthesis of hemoglobin. Most often, the disease develops as congenital or acquired. At the genetic level, anemia occurs mainly in boys.

The disease can also be transmitted in an autosomal dominant manner. This anemia is called When iron is poorly absorbed in the body, it is deposited in the internal organs, which leads to sideroblastic anemia. If there is too much iron, the functioning of the liver, kidneys and heart muscle is disrupted.

Types of disease

Anemia of this type is divided according to severity, as well as the reason for its appearance and clinical picture. There are several types of sideroblastic anemia:

1. Hereditary. The disease is inherited as a result of gene mutation. This pathology is caused by an abnormality in the metabolic process with the participation of vitamin B6 and aminolevulinic acid. The disease makes itself felt after birth or during adolescence.
2. Congenital. This form is isolated separately, although to some extent it belongs to the hereditary species. It's typical here high content erythrocyte coproporphyrin.
3. Acquired. Appears as a result of adverse effects chemical substances. Among them are ethanol, lead, and cyclosyrine.

Problems with iron synthesis also occur due to tumor processes in organism. Approximately 1/10 of patients with sideroblastic anemia suffer from acute leukemia.

Causes of the disease

The main reason for the development of this disease is a lack of protoporphyirin, which is one of the components of the synthesis of the most important element hemoglobin. In addition to this substance, protein and iron are also involved in the creation.

The acquired form of sideroblastic anemia occurs due to the fact that the body does not receive the necessary substances in sufficient quantities. There are situations when the necessary compounds are suppressed by the medications that a person takes.

The body is depleted as a result of exposure to alcohol. Anemia may occur due to lead poisoning or ingestion strong antibiotics. The hereditary form is transmitted through a female chromosome with a damaged gene. The disease may also be caused by a disorder immune system and development

Diagnosis of sideroblastic anemia

The process of identifying this disease is quite difficult, since it is practically asymptomatic. Moreover, there is no clear clinical picture to rely on. If you look only at external signs, then diagnosing this disease is unrealistic. However, there is one way to detect sideroblastic anemia - a blood test.

They also practice examination internal organs patient to look for iron deposits. But by this time the element already causes hematological symptoms. To avoid mistakes, it is necessary to confirm the diagnosis. This is done using macroscopic examination of the bone marrow.

To minimize the risk, a biopsy is necessary. This procedure is the most effective way definition of sideroblastic anemia. It is carried out as follows: the biopsy sample is pre-stained with a special substance, and if unsynthesized iron is detected, characteristic compounds become visible.

Which specialist should I contact?

As already noted, the symptoms of sideroblastic anemia are practically undetectable. Clinical picture is also missing, and because of this certain difficulties arise. If a person feels fatigue, weakness in the body, then he, as a rule, turns to a therapist. If anemia is suspected, it is the doctor who redirects the patient to a hematologist who conducts an examination.

First, the specialist finds out the general condition of the patient, is interested in the lifestyle, the presence of bad habits, a list of past diseases, etc. If the doctor deems it necessary, he will conduct several studies. These include:

• blood test (general and biochemical);
• liver biopsy;
• analysis of the cellular composition of the bone marrow.

The hematologist, if necessary, can refer the patient to other specialists for more full examination. For example, to find out the form of anemia, you need to contact a geneticist. This doctor will determine whether there is a place to be ancestral species sideroblastic anemia. You may also need to consult a gynecologist, urologist or proctologist.

Treatment options

Before starting therapy, it is necessary to determine whether iron deposition is actually occurring. For this purpose, a desferal test is used. It is administered intramuscularly, and as a result, about 0.5-1.1 mg of iron should be excreted in the urine, and for hypochromic, hypersideremic, sideroachrestic, sideroblastic anemia - 5-10 mg.

It is worth noting that hereditary form diseases cannot be cured. Treatment is often used to suppress a gene that has begun to mutate. high doses vitamin B6. It is administered in an amount of 100 mg per day. However, the body's reaction here is almost unpredictable. During the treatment of sideroblastic anemia, the hemoglobin level should increase to normal indicators in three months. If there is no improvement during this period of time, further therapy is pointless.

Prevention and prognosis

Quite often the disease occurs as a result of lead poisoning. To prevent this, you must handle this substance carefully. When reconstructing old houses, precautions must be taken, if possible, temporarily relocating children. Do not burn or bury paint containing lead. It is best to scrape them off or remove them chemically. In addition, you need to regularly monitor the cleanliness of living quarters and comply with construction and sanitary standards.

It is impossible to cure the hereditary form of the disease. To ensure beneficial effects, it is necessary to constantly monitor blood counts, especially hemoglobin levels. This is achieved by regularly undergoing a course of therapy, which does not allow the disease to develop and maintains normal condition person.

Sideroblastic anemia (congenital or acquired) is anemia when there is excess iron in the blood. Causes include alcohol abuse, chronic myeloid leukemia or myelodysplastic syndrome. Symptoms of sideroblastic anemia include, for example, pale skin, headaches and dizziness, and a fast heartbeat. Treatment in this case depends on the type of anemia.

At iron deficiency anemia There is a lack of iron in the body. Paradoxically, sometimes this element is in abundance, but cannot be used for heme synthesis.

In this situation, it develops sideropenic syndrome, the symptoms of which often resemble those of iron deficiency anemia.

Sideroblastic anemia is rare disease. There is a congenital and acquired form.

Causes

Sideropenic anemia is associated with the formation of sideroblasts or erythroblasts with an iron ring around the nucleus. Erythroblasts are the precursors of red blood cells that typically use iron to synthesize heme.

However, if this process is disrupted, the iron accumulated in the erythroblasts is not used and is deposited in excess in the liver and spleen. Abnormal, unpigmented red blood cells (which do not contain enough hemoglobin) circulate in the bloodstream without carrying sufficient oxygen.

Sideroblastic anemia may be caused by genetic defects. This hereditary anemia is detected soon after birth, although there are cases diagnosed only in adults.

Acquired sideroblastic anemia can have many causes, the most common of which are:

• medications: Chloramphenicol, Isoniazid, Cycloserine;
• lead or zinc poisoning;
• myelodysplastic syndrome;
• alcohol abuse;
• chronic myeloid leukemia.

How does sideroblastic anemia manifest?

Symptoms arise from two main problems: the first is the appearance of small, unpigmented red blood cells in the blood that do not carry enough oxygen. The second is the accumulation of iron in organs and soft tissues, that is, secondary hemochromatosis.

Symptoms associated with tissue hypoxia include dizziness and headaches, weakness, and problems with concentration. There is pallor of the skin and mucous membranes, a feeling of constant cold, accelerated heart rate and faster breathing. Iron accumulation in the liver, spleen and other organs leads to diabetes, arrhythmia and neurological disorders.

How to recognize sideroblastic anemia?

Most important role morphology with smear, bone marrow biopsy, serum iron level, ferritin concentration and transferrin saturation play a role.

The following are changes in laboratory results characteristic of sideroblastic anemia:

• morphology revealed a decrease in the number of red blood cells, a decrease in size RBC MCV and reduced hemoglobin in the blood;
• the blood smear contains siderocytes, that is, red blood cells with extrahemoglobin iron grains;
• increased iron in the blood, increased ferritin and increased transferrin saturation.

Blood test results also indicate the presence of sideroblasts in the bone marrow.

Treatment

Treatment of sideroblastic anemia depends on its form. At congenital form a vitamin B6 supplement is used, the same applies to a coexisting folic acid deficiency.

The hereditary form responds well to such therapy—response to treatment usually occurs within a few weeks.

Acquired anemia is treated with compounds that chelate excess iron in the blood (eg, deferoxamine).

During treatment it is very important to correct image life.

Diet

The diet should exclude foods containing zinc, which increases the symptoms of the disease. Therefore, excessive consumption of liver, crustaceans, nuts, and hard cheeses should be avoided.

It is important to avoid drinking alcohol. There is no cure for congenital sideroblastic anemia, but with the right treatment and diet, you can live with it without experiencing bothersome symptoms. However, acquired forms of sideroblastic anemia are completely curable.