Introduction to congenital pure red blood cell aplastic anemia

Overview of congenital pure red blood cell aplastic anemia, also known as Diamond-Blckfan syndrome (Diamond-Blackfan anemia, DBA) is a rare congenital pure red blood cell regeneration disorder, with anemia as the main clinical manifestations, and involving multiple systems The main clinical features of the disease. In 1936, Joseph reported a pure red aplastic anemia in children, considered to be congenital or hereditary. Two years later, Diamond and Blackfan also reported the same case, and the number of cases officially reported so far has exceeded 480. Epidemiology Because DBA is quite rare, its exact incidence is difficult to determine. Retrospective studies in Europe have shown that the annual incidence of DBA in children ≤ 15 years old is about 1.5/1 million to 5.0/1 million. The disease occurs in infants and young children. Most children develop from 2 weeks to 2 years after birth. The vast majority (more than 90%) of the children are diagnosed within 1 year of age. The ratio of male to female patients is about 1.1:1. The cause of this disease is occasionally seen in siblings, suggesting that the disease is a hereditary disease. Less than 10% of patients have a family history, and most of the patients are sporadic. One third of patients are autosomal dominant, and the rest are recessive. Linkage analysis revealed that there are at least three genetic loci in DBA, two of which have been identified, 19q13.2 and 8p23.3-p22, respectively. The related pathogenic gene has been cloned in the 19q13.2 region, which is the ribosomal protein S19 (RPS19) gene. Sequence analysis revealed that approximately 25% of DBA patients had an RPS19 mutation. The pathogenesis of pathogenesis is not fully understood. Conventional colony cultures showed a significant reduction or deficiency in bone marrow erythroid progenitor cells (BFU-E and CFU-E) in DBA patients. The results of previous experimental studies indicate that there is no cell and humoral immune dysfunction associated with erythroid hematopoietic defects in DBA patients, and the bone marrow matrix supports hematopoietic function. At present, a more consistent view is that DBA patients have erythroid progenitor cells with intrinsic qualitative abnormalities, which leads to a decrease in the reactivity of various hematopoietic growth factors (HGFs) that regulate the differentiation and proliferation of erythroid progenitor cells. Since DBA has hematological abnormalities similar to those of W/Wv and sl/sld mice, it is speculated that the pathogenesis of DBA may be related to the c-kit receptor/ligand (KL) system. Another study found that DB34+ cells in DBA patients were stimulated by single or combined EPO, IL-3, IL-6 and GM-CSF, and the BFU-E yield was still low or absent. Adding KL to the above culture system was obvious. Increased BFU-E colony yield and volume suggest that there is no abnormal expression of c-kit receptor in CD34 cells. The occurrence of anemia may be caused by insufficient or lack of KL production in the body. Some people think that most DBA primary defects are not in the c-kit/KL system. Only some patients have some abnormalities in the c-kit/KL system. This reflects the heterogeneity of the disease. These abnormalities explain the development of some patients. The difference in outcome. Fit-3 ligand (FL) did not cooperate with KL to stimulate bone marrow BFU-E growth in DBA patients in vitro, and there was a low level of FL in the same body as normal, suggesting that some DBA erythroid growth is not associated with FL. The current study confirmed that DBA patients do not have SCL gene and GATA gene expression and protein structure abnormalities, but their E protein expression is significantly lower, and KL can correct this defect in vitro, so it is revealed at the molecular level that KL may promote SCL/ E protein heterodimer formation plays a role in stimulating DBA erythroid hematopoiesis. The relationship between E protein abnormalities and DBA erythroid hematopoietic defects needs further study. It has been clarified that there is no abnormality in EPO and EPO-R gene expression and protein structure in DBA patients, and there is no anti-EPO-R antibody, but it is not completely excluded from the abnormal signal transmission of EPO and EPO-R in DBA. Compared with other benign anemias (such as iron deficiency anemia) with the same degree of anemia, the serum EPO level of DBA patients is more significant. This change may have the effect of protecting the remaining erythroid progenitor cells from excessive excessive apoptosis. Important physiological significance. Clinical manifestations of anemia are the main clinical manifestations of DBA, and approximately 35% of children present with anemia at birth. Another significant clinical manifestation of congenital pure red blood cell aplastic anemia is similar to Fanconi anemia (FA), with a lighter congenital physical developmental malformation. About 1/4 of the children had mild congenital anomalies, such as squinting, nipple retraction, sacral neck, finger or rib abnormalities. Complications 1. Patients with congenital pure red blood cell aplastic anemia are more likely to have complicated malignant tumors. More than 480 patients with congenital pure red blood cell aplastic anemia reported in the literature, 12 of which were diagnosed with malignant tumors 2 to 43 years after diagnosis. There were 6 cases of acute myeloid leukemia (AML), 1 case of acute lymphoblastic leukemia (ALL), 2 cases of Hodgkin's disease (HD), 2 cases of myelodysplastic syndrome (MDS) and 1 case of hepatocellular carcinoma. 2. Long-term application of hormone therapy can be combined with developmental disorders and secondary infections. 3. Progression of the disease can lead to heart failure, and advanced blood transfusion can be secondary to hemorrhagic disease, or cardiogenic cirrhosis. Laboratory examination 1. Peripheral blood picture is positive cell dysplasia, hemoglobin 10 ~ 90g / L, the absolute value of reticulocytes is reduced, infants and young children are generally not associated with peripheral blood leukocytes and thrombocytopenia. Secondary spleen hyperfunction can lead to a reduction in whole blood cells, and there are giant changes. 2. Bone marrow hyperplasia is good, but the red line is significantly reduced, and other bone marrow cells are normal. 3. Red blood cell survival time is normal. 4. Serum iron and serum iron saturation increase, fetal hemoglobin increases, i antigen persists. 5. Blood bilirubin and fecal gallbladder excretion are normal. Other auxiliary examinations are based on the condition, clinical manifestations, symptoms, and signs to choose ECG, B-ultrasound, X-ray and other examinations. Diagnostic comprehensive literature reports, some scholars have proposed the following diagnostic criteria: 1 large cell (or positive) positive pigmented anemia occurs within 1 year of age; 2 absolute number of reticulocytes decreased; 3 active bone marrow hyperplasia, with selective red The number of precursor cells is significantly reduced; 4 the number of white blood cells is normal or slightly decreased; 5 the number of platelets is normal or slightly increased. Typical cases are not difficult to diagnose. Differential diagnosis should be differentiated from Fanconi anemia, childhood transient erythrocytosis (TEC), chronic hemolytic anemia with B19 parvovirus infection, Pearson syndrome and cartilage dysplasia syndrome, in which congenital pure red cell aplasia The differential diagnosis of anemia and FA is particularly important. Treatment of red blood cells and adrenocortical hormones is an effective treatment for children to maintain a normal life. However, due to the long course of disease, long-term red blood cells can be secondary to hemochromatosis, which requires special attention. The main comorbidities of adrenocortical hormone drugs are developmental disorders and secondary infections. 1. About 75% of patients with adrenocortical hormones respond to adrenocortical hormone therapy, but only a small number of patients can achieve sustained remission, and more than 80% of patients have an adrenal cortical hormone dependent. Clinically, the recommended dose of prednisone for the treatment of congenital pure red blood cell aplastic anemia is 2mg/(kg·d) for more than 1 month. After that, the dose and course of prednisone can be adjusted according to the therapeutic response. Apply high-dose methylprednisolone (HDMP), 100mg/(kg·d), intravenous infusion for 3 consecutive days, then gradually reduce the amount. It has been reported that 9 of 17 patients with congenital pure red blood cell aplastic anemia have long-term efficacy without maintenance dose of prednisone after treatment with methylprednisolone (HDMP). However, in view of the obvious side effects of methylprednisolone (HDMP), clinically, this therapy should be cautious. Some scholars have reported that switching to oral methylprednisolone (HDMP) can reduce its side effects. 2. HGFs have erythropoietin (rhEPO), rhIL-3 and rh Morastin (GM-CSF) alone, combined or sequential treatment of congenital pure red blood cell aplastic anemia, only rhIL-3 for some patients effective. Bastion et al used rhIL-3 in the treatment of 25 patients with congenital pure red blood cell aplastic anemia, the dose was 2.5μg Read more...

Introduction Congenital pure red blood cell aplastic anemia, also known as Diamond-Blckfan syndrome (Diamond-Blackfan anemia, DBA) is a rare congenital pure red blood cell aplastic disorder with anemia as the main clinical manifestation and involving multiple systems. The main clinical features of the disease. In 1936, Joseph reported a pure red aplastic anemia in children, considered to be congenital or hereditary. Two years later, Diamond and Blackfan also reported the same case, and the number of cases officially reported so far has exceeded 480. Epidemiology Because DBA is quite rare, its exact incidence is difficult to determine. Retrospective studies in Europe have shown that the annual incidence of DBA in children ≤ 15 years old is about 1.5/1 million to 5.0/1 million. The disease occurs in infants and young children. Most children develop from 2 weeks to 2 years after birth. The vast majority (more than 90%) of the children are diagnosed within 1 year of age. The ratio of male to female patients is about 1.1:1. The cause of this disease is occasionally seen in siblings, suggesting that the disease is a hereditary disease. Less than 10% of patients have a family history, and most of the patients are sporadic. One third of patients are autosomal dominant, and the rest are recessive. Linkage analysis revealed that there are at least three genetic loci in DBA, two of which have been identified, 19q13.2 and 8p23.3-p22, respectively. The related pathogenic gene has been cloned in the 19q13.2 region, which is the ribosomal protein S19 (RPS19) gene. Sequence analysis revealed that approximately 25% of DBA patients had an RPS19 mutation. The pathogenesis of pathogenesis is not fully understood. Conventional colony cultures showed a significant reduction or deficiency in bone marrow erythroid progenitor cells (BFU-E and CFU-E) in DBA patients. The results of previous experimental studies indicate that there is no cell and humoral immune dysfunction associated with erythroid hematopoietic defects in DBA patients, and the bone marrow matrix supports hematopoietic function. At present, a more consistent view is that DBA patients have erythroid progenitor cells with intrinsic qualitative abnormalities, which leads to a decrease in the reactivity of various hematopoietic growth factors (HGFs) that regulate the differentiation and proliferation of erythroid progenitor cells. Since DBA has hematological abnormalities similar to those of W/Wv and sl/sld mice, it is speculated that the pathogenesis of DBA may be related to the c-kit receptor/ligand (KL) system. Another study found that DB34+ cells in DBA patients were stimulated by single or combined EPO, IL-3, IL-6 and GM-CSF, and the BFU-E yield was still low or absent. Adding KL to the above culture system was obvious. Increased BFU-E colony yield and volume suggest that there is no abnormal expression of c-kit receptor in CD34 cells. The occurrence of anemia may be caused by insufficient or lack of KL production in the body. Some people think that most DBA primary defects are not in the c-kit/KL system. Only some patients have some abnormalities in the c-kit/KL system. This reflects the heterogeneity of the disease. These abnormalities explain the development of some patients. The difference in outcome. Fit-3 ligand (FL) did not cooperate with KL to stimulate bone marrow BFU-E growth in DBA patients in vitro, and there was a low level of FL in the same body as normal, suggesting that some DBA erythroid growth is not associated with FL. The current study confirmed that DBA patients do not have SCL gene and GATA gene expression and protein structure abnormalities, but their E protein expression is significantly lower, and KL can correct this defect in vitro, so it is revealed at the molecular level that KL may promote SCL/ E protein heterodimer formation plays a role in stimulating DBA erythroid hematopoiesis. The relationship between E protein abnormalities and DBA erythroid hematopoietic defects needs further study. It has been clarified that there is no abnormality in EPO and EPO-R gene expression and protein structure in DBA patients, and there is no anti-EPO-R antibody, but it is not completely excluded from the abnormal signal transmission of EPO and EPO-R in DBA. Compared with other benign anemias (such as iron deficiency anemia) with the same degree of anemia, the serum EPO level of DBA patients is more significant. This change may have the effect of protecting the remaining erythroid progenitor cells from excessive excessive apoptosis. Important physiological significance. Clinical manifestations of anemia are the main clinical manifestations of DBA, and approximately 35% of children present with anemia at birth. Another significant clinical manifestation of congenital pure red blood cell aplastic anemia is similar to Fanconi anemia (FA), with a lighter congenital physical developmental malformation. About 1/4 of the children had mild congenital anomalies, such as squinting, nipple retraction, sacral neck, finger or rib abnormalities. Complications 1. Patients with congenital pure red blood cell aplastic anemia are more likely to have complicated malignant tumors. More than 480 patients with congenital pure red blood cell aplastic anemia reported in the literature, 12 of which were diagnosed with malignant tumors 2 to 43 years after diagnosis. There were 6 cases of acute myeloid leukemia (AML), 1 case of acute lymphoblastic leukemia (ALL), 2 cases of Hodgkin's disease (HD), 2 cases of myelodysplastic syndrome (MDS) and 1 case of hepatocellular carcinoma. 2. Long-term application of hormone therapy can be combined with developmental disorders and secondary infections. 3. Progression of the disease can lead to heart failure, and advanced blood transfusion can be secondary to hemorrhagic disease, or cardiogenic cirrhosis. Laboratory examination 1. Peripheral blood picture is positive cell dysplasia, hemoglobin 10 ~ 90g / L, the absolute value of reticulocytes is reduced, infants and young children are generally not associated with peripheral blood leukocytes and thrombocytopenia. Secondary spleen hyperfunction can lead to a reduction in whole blood cells, and there are giant changes. 2. Bone marrow hyperplasia is good, but the red line is significantly reduced, and other bone marrow cells are normal. 3. Red blood cell survival time is normal. 4. Serum iron and serum iron saturation increase, fetal hemoglobin increases, i antigen persists. 5. Blood bilirubin and fecal gallbladder excretion are normal. Other auxiliary examinations are based on the condition, clinical manifestations, symptoms, and signs to choose ECG, B-ultrasound, X-ray and other examinations. Diagnostic comprehensive literature reports, some scholars have proposed the following diagnostic criteria: 1 large cell (or positive) positive pigmented anemia occurs within 1 year of age; 2 absolute number of reticulocytes decreased; 3 active bone marrow hyperplasia, with selective red The number of precursor cells is significantly reduced; 4 the number of white blood cells is normal or slightly decreased; 5 the number of platelets is normal or slightly increased. Typical cases are not difficult to diagnose. Differential diagnosis should be differentiated from Fanconi anemia, childhood transient erythrocytosis (TEC), chronic hemolytic anemia with B19 parvovirus infection, Pearson syndrome and cartilage dysplasia syndrome, in which congenital pure red cell aplasia The differential diagnosis of anemia and FA is particularly important. Treatment of red blood cells and adrenocortical hormones is an effective treatment for children to maintain a normal life. However, due to the long course of disease, long-term red blood cells can be secondary to hemochromatosis, which requires special attention. The main comorbidities of adrenocortical hormone drugs are developmental disorders and secondary infections. 1. About 75% of patients with adrenocortical hormones respond to adrenocortical hormone therapy, but only a small number of patients can achieve sustained remission, and more than 80% of patients have an adrenal cortical hormone dependent. Clinically, the recommended dose of prednisone for the treatment of congenital pure red blood cell aplastic anemia is 2mg/(kg·d) for more than 1 month. After that, the dose and course of prednisone can be adjusted according to the therapeutic response. Apply high-dose methylprednisolone (HDMP), 100mg/(kg·d), intravenous infusion for 3 consecutive days, then gradually reduce the amount. It has been reported that 9 of 17 patients with congenital pure red blood cell aplastic anemia have long-term efficacy without maintenance dose of prednisone after treatment with methylprednisolone (HDMP). However, in view of the obvious side effects of methylprednisolone (HDMP), clinically, this therapy should be cautious. Some scholars have reported that switching to oral methylprednisolone (HDMP) can reduce its side effects. 2. HGFs have erythropoietin (rhEPO), rhIL-3 and rh Morastin (GM-CSF) alone, combined or sequential treatment of congenital pure red blood cell aplastic anemia, only rhIL-3 for some patients effective. Bastion et al used rhIL-3 in the treatment of 25 patients with congenital pure red blood cell aplastic anemia, the dose was 2.5μg Read more...