Congenital dyserythropoietic anemia in children

Introduction to children with congenital erythropoiesis abnormal anemia Congenital erythropoietic anemia (CDA), also known as congenital red blood cell aplastic anemia, is a rare autosomal hereditary disease characterized by anemia with reticulocyte reduction and erythroid ineffective hematopoiesis. Often liver, splenomegaly, shortened red blood cell life, jaundice and gallstones, etc., CDA is characterized by: 1 ineffective hematopoiesis (red blood cells and young red blood cells in the bone marrow destruction). 2 There are more multinucleated red blood cells in the bone marrow. 3 secondary hemochromatosis (hemochromatosis). basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: jaundice, gallstones, cirrhosis, hemochromatosis

Pediatric congenital erythropoiesis abnormal anemia

(1) Causes of the disease

1. Classification: According to morphological and serological characteristics, CDA is divided into the following three types: type I: giant red blood cells with giant bone marrow changes and internuclear chromatin bridge, type II: positive red blood cells or giant red blood cells with bone marrow Dual-nuclear red, multi-nuclear red, nuclear fragmentation, etc., acid hemolysis test positive, type III: giant red blood cells with multinuclear red (macro nucleated red blood cells) with more than 12 nucleus of bone marrow, CDA type I and type III are mainly diagnosed by morphological features CDA type II, also known as HAMPAS, is the abbreviation of hereditary erythroblastic multinuclearity with a positive acidified serum test (HAMPAS). In addition, more than 50 patients reported in the literature have disease characteristics. The above classification.

2. Etiology: CDA is an autosomal hereditary disease, but it is not clear that the formation of red blood cell colonies in vitro is normal, but multinucleated red blood cells can be seen, which may be caused by structural abnormalities of the erythroid nuclear membrane and cytoplasmic membrane. Increased damage and reduced DNA.

(1) CDAI type: It is an autosomal recessive hereditary disease, and more than 100 cases have been reported. Some of them have a blood relationship, which is a familial disease. The onset age ranges from birth to adult, the average age is 10 years old, and the ratio of male to female is 1.1. : 1.

(2) CDA type II (HEMPAS): It is the most common type of CDA. It has been reported in more than 200 cases. Some patients have blood relationship and are autosomal recessive hereditary diseases. The age of onset is from birth to adult. The average age is 14 years old and the male to female ratio is 0.9:1.

(3) CDA type III: It is a rare type. More than 70 cases have been reported so far, mainly from about 16 families. The ratio of male to female is 0.8:1. The average age at diagnosis is 24 years old, which can occur from birth to old age.

(4) Other types of CDA: CDA is difficult to identify, and more than 50 patients cannot be classified into the above 3 types. Therefore, the concept of variant is proposed. In the literature, CDAIV is characterized by bone marrow morphology similar to CDA II. 10%40% of nucleated red blood cells are binuclear, acid hemolytic test is negative, and 1 case is autosomal dominant. Unlike CDAII type, i-antigen on erythrocyte surface does not increase, most patients have mild anemia symptoms. The prognosis is relatively good.

(two) pathogenesis

The patient's iron metabolism is accelerated, which is 10 times higher than that of normal people. The red blood cells in the bone marrow proliferate vigorously, resulting in increased intestinal absorption of iron, increased transferrin saturation, decreased iron utilization, increased iron clearance, and destruction of young red blood cells in the bone marrow. Increased, only 30% of red blood cells can enter the peripheral blood, which further proves that erythroid ineffective hematopoiesis, increased indirect bilirubin and lactate dehydrogenase, decreased haptoglobin levels, increased transferrin saturation, and mild red blood cell lifespan Shortened, some patients increased HbA2, globin chain synthesis was unbalanced, non-/ chain ratio decreased (0.5-0.7), acid hemolysis test was negative, erythrocyte i antigen titer was normal, CDAI type defect was at stem cell level, but cells The amount of CFU-E and BFU-E cultured is normal because there are mixed clones of normal and abnormal cells in the bone marrow, suggesting that the abnormal expression of the progeny of each stem cell is diverse, and the CDAI type gene (CDAN1) is located at 15q15. .1 to 15.3, but some patients did not find this gene localization, suggesting genetic heterogeneity.

Pediatric congenital erythropoiesis abnormal anemia prevention

The cause is still unclear, and attention should be paid to the prevention of genetic diseases.

Pediatric congenital erythropoiesis anemia complication Complications jaundice gallstone cirrhosis hemochromatosis

About half of the red blood cells are fragile, intermittently appearing jaundice, liver and splenomegaly, visible bile duct obstruction, can be complicated with gallstones, cirrhosis; long-term disease can be secondary to hemosiderosis and hemochromatosis; can be complicated by endocrine function Disorders, such as gonadal development disorders, hypothyroidism and non-familial diabetes. Can be short and short. Can be combined with fingers, abnormal toe, combined with myeloma.

Children with congenital erythropoiesis abnormal anemia symptoms common symptoms red blood cell life shortening erythrocytosis bile duct obstruction jaundice hemosiderosis splenomegaly

The age of onset and the severity of anemia vary greatly. It is often diagnosed after the age of 10, the onset is slow, and more often due to anemia, and intermittent changes in jaundice and urine color, liver and splenomegaly, bile duct obstruction, The long-term disease may be secondary to hemosiderosis and hemochromatosis. Although hemosiderin is associated with multiple blood transfusions, it has been proved that the main cause of iron metabolism is hyperplasia, and the intestinal tract is iron. Increased absorption, increased transferrin saturation, decreased 59Fe utilization, increased clearance, some patients have shortened red blood cell life, visible gland developmental disorders in adult patients, hypothyroidism and non-familial diabetes, individual patients can continue Liver cirrhosis, anemia and severity, showing non-specific deformed red blood cells, reticulocytes are reduced in proportion to anemia, white blood cells and platelets are normal, serum is not bound to bilirubin, urinary bile is often positive, and cell bodies are visible in bone marrow. Large multinucleated young red blood cells, according to changes in blood, bone marrow and biochemistry, the disease is divided into 4 types, each type of special point.

The most common type II, accounting for about 60% of the disease, is also known as hereditary erythroblastic multinuclearity with a positive acidified serum (HEMPAS), common anemia and mild jaundice, liver, Splenomegaly, about half of the erythrocyte fragility is increased, red blood cell shape is irregular, polychromatic, occasionally nucleated red blood cells, red blood cells in the bone marrow increase, visible binuclear and multinucleated young red blood cells, electron microscopic examination shows that some red blood cells have double cell In the serosa, it is speculated that this change is the cause of the cell's inability to divide. It is also known that the Geshe-like cells are positive for acid hemolysis, and hemolysis is increased in anti-i and anti-I serum. Glycosylation of this type of erythrocyte membrane protein has been reported. Abnormal effect, Beijing Children's Hospital in 1979 saw a 5-year-old boy with the above-mentioned typical symptoms and laboratory test results, more polynuclear, young red blood cells in the bone marrow.

Examination of abnormal anemia of congenital erythropoiesis in children

Blood picture

(1) CDAI type: blood routine examination showed hemoglobin 20 ~ 150g / L, an average of 90g / L, reticulocytes were 1% ~ 7%, 72% of patients increased MCV, red blood cell size is uneven, visible all kinds of abnormal red blood cells , spotted red blood cells, occasionally visible Cabot ring, white blood cells and platelets normal.

(2) CDA type II (HEMPAS): blood routine examination showed a large difference in hemoglobin concentration, mean hemoglobin 95g / L, range 30 ~ 150g / L, MCV is normal, reticulocytes are normal or slightly elevated, an average of 4%, blood The smear shows that the red blood cells are obviously uneven in size, and the pigmentation is uneven. Differently shaped red blood cells include teardrop-shaped red blood cells, irregularly shrunken cells, nuclear fragmentation, spotted red blood cells, occasionally spherical red blood cells, and sometimes nucleated red blood cells, and Compared with CDAI type, the life of red blood cells was significantly shortened, and the activities of serum bilirubin and lactate dehydrogenase were increased.

(3) CDAIII type: blood routine examination for mild to moderate giant cell anemia, hemoglobin average 95g / L, range 40 ~ 140g / L, peripheral blood smear can be seen red blood cell size uneven, abnormal red blood cells, point color red blood cells and large Red blood cells are easy to see, red blood cell life is slightly shortened, serum bilirubin and lactate dehydrogenase are increased, haptoglobin is decreased, Ham test is negative, mature red blood cells and anti-i antibody coagulate, but weaker than CDAII type, some patients have beads Protein synthesis imbalance.

2. Bone marrow examination: showing erythroid hyperplasia, accounting for more than 75%, of which 10% to 40% are multinucleated red blood cells, more than 2 nucleus can appear, visible multi-tropic red blood cells, dual-nuclear red, multi-nuclear red, nuclear sprouting, nuclear Irregularities and nuclear fragmentation are easy to see. More than 2% of nucleated red blood cells show a fine chromatin bridge, which connects two nucleus of almost completely isolated cells. Electron microscopy shows the presence of mixed clones of normal and abnormal cells, about 50 % of nucleated red blood cells have Swiss-cheese abnormalities, that is, multiple sea-like regions appear in the heterochromatin region with abnormal electron density. Most of these cells have severe DNA, and RNA and protein synthesis are reduced or stagnant and will be in the bone marrow. Macrophage phagocytosis, nuclear membrane intussusception, cytoplasm and cytoplasmic organelles enter the nucleus of nucleated red blood cells, nucleated red blood cells peripheral chromatin condensation, nuclear membrane pore abnormalities, iron in the cytoplasm Sinking, in vitro cell culture can form normal and abnormal nucleated red blood cell clones, suggesting hematopoietic stem cell defects. The pathogenic genes of Swedish family CDAIII patients are located at 15q21-25, routine X-ray, B-ultrasound an examination.

Diagnosis and diagnosis of congenital erythropoiesis abnormal anemia in children

According to clinical manifestations and laboratory tests, the diagnosis of CDA is mainly based on the following points: benign, positive pigmentation, refractory simple anemia with persistent or intermittent jaundice. Reticulocytes are not high; bone marrow erythroids are obviously proliferating, and there are typical morphological changes, and granulocytes and megakaryocytes are normal. There may be abnormalities in the thalassemia-like erythrocyte globin peptide chain, changes in HEMPAS antigen and i antigen. There may be a positive family history.

Must be differentiated from other hematopoietic anemia, such as aplastic anemia, erythroleukemia, myelosclerosis and nucleoprotein synthesis disorders including vitamin B12 or folate deficiency, type II serum acid hemolysis test positive, with paroxysmal nocturnal hemoglobin Urine identification, the identification between the various types is sometimes difficult.

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