sideroblastic anemia in children
Introduction
Introduction to pediatric iron erythrocyte anemia Iron erythroblastic anemia (SA) is an anemia caused by a group of different heme synthesis disorders and iron utilization. It is characterized by the presence of a large number of "ring" iron red blood cells in the bone marrow, and iron treatment is ineffective. The disease is divided into acquired and hereditary, and acquired is divided into primary and secondary. basic knowledge The proportion of illness: 0.002% Susceptible people: children Mode of infection: non-infectious Complications: hemochromatosis diabetes cirrhosis cardiomyopathy
Cause
Pediatric iron erythrocyte anemia cause
(1) Causes of the disease
Hereditary: divided into sexual or autosomal recessive inheritance.
1.X chromosome sex inheritance
It is the most common type. Only males in this family have anemia, and female carriers generally have no anemia, but the red blood cell population is often markedly biphasic. In addition, only the female neutrons are sick, and may be X-linked dominant inheritance, because males cannot survive, and no male patients appear. At present, X-sexual inheritance has not been fully concluded.
2. Autosomal inheritance
Some families show vertical inheritance between father and son, while others find that brothers and sisters have the same disease, and the extent is the same, suggesting that the genetic pattern is autosomal recessive or autosomal dominant. Acquired: Acquired can be divided into primary and secondary according to the cause. Primary: The cause is unknown, more common in young adults. Although the cause is unknown, the possibility of exposure to harmful chemical or physical factors can be completely ruled out. Secondary: a variety of cytotoxic drugs, such as the treatment of malignant tumors and leukemia drugs such as nitrogen mustard, cyclophosphamide. 6-mercaptopurine, cytarabine, methotrexate and doxorubicin. Other chemical factors such as benzene, paint, gasoline, pesticides, etc. are also associated with aplastic anemia. Various ionizing radiation, acute and chronic infections, including bacteria (typhoid fever, etc.), viruses (hepatitis, EBV, CMV, B19, etc.), parasites (malaria, etc.). It can also be secondary to various blood diseases. Certain diseases can cause abnormal iron metabolism, such as myelodysplastic syndrome, leukemia, lymphoma, and other systemic cancer, rheumatoid arthritis, porphyria, pernicious anemia, malabsorption syndrome, hemolytic anemia, mucus Sexual edema, etc., these diseases can cause abnormal iron metabolism, and complicated by anemia of iron granule cells. Whether the hereditary or acquired children are further responsive or ineffective in the effect of the therapeutic response to pyridoxine (vitamin B6), the hereditary responder to vitamin B6 is preferred.
(two) pathogenesis
Hereditary
In the process of heme biosynthesis, when some enzymes are lacking or obstacles are generated in the biochemical process, excessive accumulation of non-heme iron in the red blood cells can be caused, and pathological iron red blood cells are produced. In the mitochondria of erythrocytes, as a first step in the biosynthesis of porphyrins, glycine and succinate coenzyme A bind to -amino gamma keto valeric acid (ALA). Pyridoxine (vitamin B6) is converted in vivo to the biologically active pyridoxal 5-phosphate (PLP), which is involved as a coenzyme indispensable for the synthesis of ALA. There is evidence that the disease is due to genetic defects in this biochemical process, and the biochemical defects of each family are not necessarily the same.
Acquired
PLP antagonists inhibit RNA synthesis in bone marrow cells and, more importantly, inhibit mitochondrial proteins, including the synthesis of certain cytochromes and cytochrome oxidases. May be related to the damage of cytochrome in mitochondria, can inhibit the conversion of pyridoxine to PLP, inhibit the ALA dehydratase heme synthase and inhibit the conversion of coproporphyrinogen III to protoporphyrin III, so it can be used in chronic lead poisoning. Iron granule anemia occurs.
Pathological change
A small amount of iron is found in the cytoplasm of young red blood cells in normal human bone marrow. When stained with iron, 30% to 60% of young red blood cells have fine iron particles, but the number is only 1 to 2, and the maximum is no more than 5. The young red blood cells of this disease not only contain large iron particles, but also a large number of them and the quality is pathological. Under the light microscope, iron particles are seen to be annular or at least 1/3 annular around the nucleus of the young red blood cells. Under abnormal electron microscopy, the abnormal mitochondria deformed, swelled, and ruptured. Iron was deposited in the mitochondria of the mitochondria by dust or plaque, and lost the ultrastructure of ferritin or hemosiderin. Due to iron deposition, the young and middle red blood cells are also inhibited from entering the cell proliferation cycle, resulting in red blood cell ineffective hematopoiesis.
Prevention
Pediatric iron erythrocyte anemia prevention
1. Pay attention to the rational use of drugs to avoid exposure to harmful chemicals such as benzene.
2. During pregnancy, we must pay attention to the influence of various adverse factors, do the corresponding birth check, and have a family history to conduct genetic counseling.
Complication
Pediatric iron granulocyte anemia complications Complications, hemochromatosis, diabetes, cirrhosis, cardiomyopathy
Excessive iron is a common complication of this disease, which can be combined with hemochromatosis, diabetes, cirrhosis, cardiomyopathy, etc. due to massive deposition of iron. In the advanced stages of the disease, it can lead to death. In addition, too much iron can lead to low immune function and can be killed by concurrent infection.
It is often seen that the liver and spleen are mild to moderately enlarged, and the liver function is normal or mildly abnormal. Severe cases can be complicated by heart failure, liver insufficiency and so on.
About one-third of patients develop diabetes and occasionally skin pigmentation. Children with severe anemia and children with growth retardation.
Can be complicated by bleeding in the digestive tract, urinary tract.
Symptom
Pediatric iron red blood cell anemia symptoms common symptoms skin mucosa pale liver splenomegaly red blood cell malformation jaundice
The clinical manifestations of hereditary or acquired iron erythroblastic anemia were similar. The course of the disease is slow and a benign process, often treated with anemia. There are different degrees of pale or mild jaundice in the skin mucosa, and half of the spleen or liver is large but light, so sometimes it can not be touched. Bleeding performance is only occasional.
Clinical symptoms:
1. Anemia is the main symptom and sign of the disease. Often the skin is pale, and some patients have dark black skin. Weak, moving, heart, and shortness of breath. The liver and spleen are slightly enlarged.
2. Hepatosplenomegaly is significant when hemochromatosis occurs (ie, hemosiderin deposition). Heart, kidney, liver and lung dysfunction can occur when hemochromatosis occurs, and a small number can develop diabetes.
3. Due to long-term anemia, severe malnutrition, mental retardation, and low immunity are caused.
Clinical classification:
1. Hereditary: male onset, female as carrier. A small number of autosomal inheritors can be affected by both men and women. Early symptoms are weak and weak. Anemia is mostly moderate, but the difference is very large, and even some relatives have different degrees of anemia.
2. Acquired: Both men and women can develop the disease. Mainly manifested as anemia, the anemia caused by drugs can be quite serious, and even need blood transfusion. The onset is slow.
(1) Primary: The onset is concealed and the condition progresses slowly. With anemia as the main performance, the degree of anemia is different.
(2) Secondary: In addition to the characteristics of this disease, patients also have symptoms of primary disease or a history of applied drugs.
Examine
Examination of iron-like erythrocyte anemia in children
1. Blood: low pigmented anemia, usually moderate anemia (hemoglobin at 70-90g / L), a small number of severe anemia (hemoglobin 30-60g / L). Hemoglobin is mostly in the range of 70-100 g/L (7-10 g/dl), and can be seen as low as 30 g/L (3 g/dl). Most of the mature red blood cells in hereditary origin are typical, low-numbered small pigment cells. Acquired people can see normal pigmented red blood cells or red blood cells at the same time. Reticulocytes are reduced, or the increase is not obvious. White blood cell and platelet counts are generally normal, but there may be inhibition in acquired patients.
2. Bone marrow examination: The red blood cell system is obviously proliferated in the bone marrow slices, mainly in the middle and young red blood cells, and there may also be giant mega-like changes (the mega-erythrocyte changes can be seen in those who respond to folic acid). The cytoplasm showed vacuoles, less pulp, and lack of hemoglobin formation. Pathological iron red blood cells and "circular" iron red blood cells were stained with Prussian blue, up to 40%. The granulosa and megakaryocytes are normal.
3. Blood biochemistry: serum iron content increased to 35.8mol/L (200g/dl); transferrin saturation increased to over 90%; serum total iron binding capacity and/or unsaturated iron binding capacity decreased . Plasma iron conversion rate increased. Unbound bilirubin in the blood is slightly elevated. The neutrophil alkaline phosphate plum score is reduced.
4. Erythrocyte free protoporphyrin: reduced in hereditary, indicating a defect in ALA synthase or coproporphyrinogen oxidase. Erythrocyte free protoporphyrin can be increased in both hereditary and idiopathic acquired cases when heme synthase or iron chelatase is defective. Regular B-ultrasound and X-ray examination.
The survival time of red blood cells measured by 5.51Cr is normal or slightly shortened, and the average life span of red blood cells is 40 to 100 days.
6. Increased excretion of uric acid (48-dihydroxyquinolinic acid) and/or canine quinolinic acid in urine indicates abnormal metabolism of tryptophan.
7. The FEP in the red blood cells is reduced or at the lower limit of normal, and the FEC in the red blood cells is mostly normal. In cases where pyridoxine treatment is ineffective, FEC can be high and FEP is significantly reduced.
Diagnosis
Diagnosis and diagnosis of iron-like anemia in children with iron
diagnosis:
According to the age of the disease, the characteristics of the disease, it is generally not difficult to make a diagnosis of iron blast cell anemia.
Diagnose based on:
1. Low pigmented anemia, reticulocytes are not high.
2. Bone marrow erythroid cell proliferation, bone marrow smear stained with iron after the emergence of a large number of "ring" iron red blood cells.
3. The serum iron content is increased, and the iron saturation is greater than normal. Diagnosis is generally not difficult, and misdiagnosis and missed diagnosis are mostly due to no examination of bone marrow iron staining. If the child has a recent medication history or is taking medication, he should ask the name, dosage and primary disease of the drug. For example, if the drug or preparation is easy to take the disease, most of the symptoms will disappear soon after the withdrawal. Trial withdrawal can also be used as a counter-diagnosis of the disease secondary to drugs or poisons.
Differential diagnosis:
1. Identification of two kinds of iron granule anemia cells must be based on detailed medical history and physical examination, as well as family investigation. Acquired often has obvious primary causes.
2. Identify iron deficiency anemia with other types of anemia: Iron deficiency anemia is an anemia that occurs when iron stores in the body do not meet the needs of normal erythropoiesis. It is due to insufficient iron intake, reduced absorption, increased demand, iron utilization barriers or excessive loss. Morphological manifestations of small cell hypochromic anemia. Thalassemia: There is a family history, a large number of target red blood cells can be seen in the blood, hemoglobin A2 is increased, serum ferritin and bone marrow can increase iron. Chronic inflammatory anemia: normal iron binding is reduced or decreased, serum ferritin is increased.
3. Identification of diseases similar to other similar manifestations SA is easily confused with RAS in MDS, and attention should be paid to identification. MDS is a group of stem cell abnormal syndrome, and the hematopoietic system is characterized by the morphological characteristics of the differentiation of erythroid, granulocyte and megakaryocyte cell lines, the so-called "pathological hematopoiesis". Anemia is a large cell or positive cell positive pigmentation, while hereditary SA is mostly hypopigmented small cell anemia, no pathological hematopoietic manifestations, except for the red blood cell line, other hematopoietic cells are not abnormal. In addition, only a small number of RAS responded to vitamin B6 treatment, while hereditary SA was effective in some cases with large doses of vitamin B6.
