congenital dyserythropoietic anemia
Introduction
Introduction to abnormal anemia of congenital erythropoiesis Congenital erythropoietic anemia (CDA) is a rare hereditary erythroid cell lineage-ineffective hematopoietic familial disease. Its clinical features are chronic, refractory mild or severe anemia with persistent or intermittent jaundice. Bone marrow is characterized by ineffective hematopoiesis, multinuclear, nuclear fragmentation and other morphological abnormalities in the red blood cell line. basic knowledge The proportion of illness: 0.003% Susceptible people: young children Mode of infection: non-infectious Complications: cholecystitis, hemochromatosis
Cause
Causes of abnormal anemia of congenital erythropoiesis
(1) Causes of the disease
Most scholars believe that CDA type I, type II is autosomal recessive, and type III is autosomal dominant.
(two) pathogenesis
The pathogenesis is still unclear. In vitro studies suggest that the hematopoietic abnormalities of various types of CDA are mainly in the red blood cell line itself, the hematopoietic microenvironment and the granulocyte, and the megakaryocyte cells have no obvious abnormalities; the morphologically normal or no abnormal red blood cells and abnormal morphology The red blood cells are all from the same clone; nuclear fragmentation, multinuclear may be related to abnormal nuclear protein synthesis, abnormal or lack of nuclear membrane, widening of nuclear pores, disorder of cytoplasmic and nuclear material distribution.
Prevention
Congenital erythropoiesis abnormal anemia prevention
Pay attention to diet, it is best to eat some patients with good digestion.
Complication
Congenital erythropoiesis abnormal anemia complications Complications cholecystitis hemochromatosis
Common complications are cholecystitis and secondary hemochromatosis.
Symptom
Congenital erythropoiesis abnormal anemia symptoms common symptoms lymphadenopathy hepatosplenomegaly
1. The CDAI type has been reported to more than 30 patients so far. Brothers and sisters can be diagnosed at the same time or in succession. However, the second and second generations have not been found in the same family. The incidence can be after birth (onset of neonatal jaundice), early childhood, but most adults. Onset, physical examination showed splenomegaly and jaundice, and anemia was mild.
2. CDA type II In 1969, Crookston named this model as hereditary erythroblast multinuclearity with positive acidified serum test (HEMPAS). This type is relatively common and has been reported in 55 families. 84 patients, the main clinical manifestations of positive cell anemia, jaundice, hepatosplenomegaly, the degree of anemia varies from person to person, light patients (60%) in childhood, hemoglobin up to 110g / L, early no anemia symptoms, to Anemia occurs only after adulthood. About 25% of patients have relatively serious illnesses. Infants and young children need regular blood transfusions. Some patients have special faces and the skull double-layer is widened.
3. CDA type III This type was first reported. The case described by Wolf et al. in 1951 belongs to this type. It has been reported that 23 families of 4 families have the same family, and the same family can be infected in different generations, suggesting that it is autosomal. Sexual inheritance, clinical manifestations of moderate to mild positive pigmentary anemia, commonly used to promote blood drug treatment is not effective, but the general condition is stable, and the prognosis is good, the body can be seen jaundice, no liver, spleen, lymph nodes.
In addition to the above three types, since the 1970s, there have been reports of CDA between Types I and II. Others have reported the so-called CDA type IV, whose main features are: bone marrow morphology is similar to CDAII type, but " i" antigen is normal.
Examine
Examination of abnormal anemia of congenital erythropoiesis
1. CDAI type (1) Peripheral blood: cell size is uneven, abnormal shape, spot color, carbomer ring are obvious, white blood cells and platelets are normal.
(2) Bone marrow: The red line is obviously hyperplasia, and the binuclear red blood cells, multinucleated red blood cells and giant red blood cells can be seen. The characteristic change is the Feulgen test positive internuclear chromatin bridge connecting two nucleated red blood cells. Under electron microscope, the chromatin is sponge. The shape is not uniform, and the nucleus changes like "cheese".
(3) serum indirect bilirubin can be increased: urinary biliary primordia.
(4) Serum iron increased or normal: the ratio of erythrocyte globin alpha to non-alpha peptide chain increased, showing inclusion bodies, and the etiology of other specific hemolytic anemia was negative.
2.CDAII type
(1) Peripheral blood: The red blood cell size is also uneven, the red blood cells are shaped, the red blood cells are colored, and under one phase microscope, the characteristic changes of red blood cells are seen, that is, the red blood cells are ghosted; the ghost shadow area is observed by the double-layer film under electron microscope. composition.
(2) Bone marrow: hyperplasia is obviously active, binuclear red blood cells account for 10% to 40% of erythroid, mostly young red; unlike type I, rare red blood cells are rare, and some patients can see reticular cells phagocytizing red blood cells.
(3) PNH erythrocyte-like changes in mature red blood cells: sensitive to acidified serum, which has been shown to be due to the presence of HEMPAS antigen on the surface of CDA type II erythrocyte membrane, and the antigen-antibody reaction activates the classical complement pathway, but its sensitivity to acidified serum PNH is poor, sucrose test never occurs hemolysis, further studies have also shown that HEMPAS antigen is caused by genetic abnormality of N-acetylglucosaminyltransferase II, because the abnormality of this enzyme leads to abnormalities in the constituent glycoproteins of cell membrane, especially Band 3, band 4, 5, and possibly glycoprotein A abnormalities, another serological abnormality is the increase in "i" antigen on the surface of red blood cells.
3.CDA type III
(1) Peripheral blood: Mature red blood cells are obviously uneven in size, and there are huge red blood cells, nucleated red blood cells, normal or low reticulocyte counts, and normal white blood cells and platelets.
(2) Bone marrow: The erythroid is obviously hyperplasia, and there are huge changes in nucleated red blood cells at each stage. Some nucleated red blood cells have a diameter of 50-60 m, containing 10-12 nucleoli, two cores, three cores, multinucleated red blood cells, and nucleus. Fragmentation is common, and the morphology of granulocytes and megakaryocytes is generally normal.
(3) elevated serum iron levels: serum indirect bilirubin increased, urinary biliary primordia increased.
(4) Increased erythrocyte globin peptide chain: visible inclusion body, red blood cell life, saline osmotic fragility test, acidified serum hemolysis test, Coombs test were normal.
According to the condition, choose B-ultrasound, electrocardiogram, X-ray and other examinations.
Diagnosis
Diagnosis and diagnosis of abnormal anemia of congenital erythropoiesis
The diagnosis of CDA is mainly based on the following points: benign, positive pigmentation, refractory simple anemia with persistent or intermittent jaundice; reticulocyte is not high; bone marrow erythroid is obviously hyperplasia, and there are typical morphological changes, granulocyte, The megakaryocyte is normal, may have an abnormality of the thalassemia-like erythrocyte globin peptide chain, and changes in HEMPAS antigen and i antigen may have a positive family history.
Differential diagnosis
1. CDA should be differentiated from thalassemia because both are familial, with anemia, jaundice and globin peptide chain abnormalities, but thalassemia patients may have so-called "thalmy face", reticulocyte increase, red blood cell life Significantly shortened, the effect of spleen treatment is good; and CDA can have chromatin "bridge", red blood cell "ghost shadow", huge / multi-nuclear red blood cells and HEMPAS antigen and i antigen changes, etc., thereby distinguishing between the two diseases, of course If you do a red blood cell genetic test on a typical CDA patient in the future, it will definitely help to identify it.
2. CDA type II should be differentiated from non-onset paroxysmal nocturnal hemoglobin (PNH). Both of them may be positive for acid hemolysis test, but the mechanism of PNH red blood cells sensitive to complement is distinct from CDA: PNH is due to phosphatidyl Abnormality of the alcohol glycoside class A (PIG-A) gene results in a small amount of phosphatidylinositol (GPI) anchoring protein on the blood cell membrane, which in turn affects complement regulation; while CDA is due to HEMPAS antigen, it can be determined by measuring complement on erythrocyte membrane. In addition to the regulatory proteins (DAF, CD59), PNH disease in hematopoietic stem cells, especially non-onset type, often manifests as complete cytopenia and poor myeloproliferative, which can also be distinguished from CDA type II.
3. The identification of CDA and megaloblastic anemia mainly depends on the medical history (including nutritional history and family history) and folic acid or (and) vitamin B12 treatment. The identification of CDA and myelodysplastic syndrome and leukemia is mainly based on the latter two. Malignant diseases often involve the whole marrow (whole blood cells), and there are pathological, histochemical, chromosome and even oncogene abnormalities.
