Pediatric beta thalassemia
Introduction
Introduction to Pediatric Beta Thalassemia Betathalassaemia (referred to as thalassemia), also known as thalassemia, should be called "globin-producing anemia" according to the National Medical Terminology Committee. It is because the synthesis of one or more globin peptide chains is blocked or completely inhibited, resulting in abnormal composition of Hb components, causing chronic hemolytic anemia. According to different types of globin gene deletions or defects, the corresponding inhibition of bead chain synthesis is different, and the thalassemia can be divided into -thalassemia; -thalassemia, -thalassemia, -thalassemia and Rare beta-thalassemia; the previous two types are common, all kinds of thalassemia can be combined with each other, can be combined with various abnormal Hb (such as HbE / beta thalassemia), this group of diseases, also known as thalassemia syndrome , are all autosomal incomplete dominant inheritance. basic knowledge Sickness ratio: 0.0001% Susceptible people: infants and young children Mode of infection: non-infectious Complications: jaundice edema anemia pneumonia liver fibrosis
Cause
Pediatric beta thalassemia cause
(1) Causes of the disease
Cause
The -globin gene is located in the short arm 1 region 2 band of chromosome 11 (abbreviation: 11P12). Most of the disease except for a few nucleotide deletions, point mutations (single nucleotide substitution, Due to the increase or absence, 100 types of gene mutations have been found in the world. There are 20 species in China (Table 1). Those who are inhibited by -chain synthesis are called beta thalassemia; those who are completely inhibited by -chain are called "o thalassemia", the inhibition of peptide synthesis involves chain, called marine anemia ( or o), the two allele mutations on the chromosome are the same homozygous; allele mutations are different "Double heterozygous"; only one mutant on a homologous chromosome is called a "heterozygous".
2. Classification
According to the heterozygote and homozygote produced by the gene defect, the clinical manifestations are also different. According to the severity of the disease, thalassemia can be classified into three types: heavy, light and intermediate.
(1) severe beta thalassemia: severe -mediterranean anemia major, also known as Couleys anemia, which is homozygous for beta thalassemia, double heterozygosity for beta and beta thalassemia or homozygous for beta thalassemia Or o homozygote, is a common thalassemia in China. Both parents of this disease are heterozygous -thalassaemia, and their children have a severe -thalassemia rate of 25%, 50% are heterozygous, and the remaining 25% It is normal.
(2) Intermediate beta thalassemia: -mediterranean anemia intermedia includes: gene homozygote, some 0/ double heterozygotes, atypical beta thalassemia heterozygotes, combined with alpha anemia And thalassemia, its clinical manifestations are between heavy and light, featuring:
1 The age of onset is relatively late (usually 4 to 5 years old).
2 moderate anemia, Hb 60 ~ 90g / L.
3 mild hepatosplenomegaly.
4 Peripheral blood smear red blood cell morphology similar to heavy.
The 5HbF content is increased, and HbA2 can be slightly higher, normal or reduced.
6 The amount of blood transfusion is small or blood transfusion is not necessary to maintain life; family survey confirmed the above gene delivery.
Atypical beta-thalass heterozygote: refers to the locus control region (LCR) located in the distal region of the -globin gene. These are not molecular defects in the -chain (atypical -thalassemia gene) and typical The beta thalassemia gene combines to form a double heterozygote.
(3) Light beta-thalassemia: -mediterranean anemia minor or trait is a 0, or gene, including a double mutant heterozygote (referred to as the nucleotide sequence of the diseased -globin gene) At the same time, there are two heterozygous states of the mutation point, such as [TATA box-28(AG)CDl7(AT)/N], which is mainly characterized by mild small cells, hypopigmentemia, especially in infancy. There may be mild jaundice and splenomegaly.
(two) pathogenesis
Many pathophysiological and clinical manifestations of -thalassemia are related to the imbalance of globin chain synthesis. Since the synthesis of -strand is inhibited, the synthesis of HbA(22) can be reduced or absent, in heterozygotes, excess -chain Binding to the compensated chain increases AbA2 (22). In the homozygote, the chain is relatively increased due to the significant decrease of the chain, and the excess chain is combined with the chain. Therefore, HbF (22) becomes the main red blood cell. The Hb component, because HbF has higher oxygen affinity than HbA, it is not easy to release oxygen in tissues, so patients often have tissue hypoxia, hypoxia causes a large amount of erythropoietin secretion, stimulates bone marrow hematopoietic function, and red bone marrow is extremely dilated. This causes a series of bone changes.
Due to the imbalance between the and chains, the excess chain can be polymerized into extremely unstable 2, 3, or 4, and the variability is deposited in the red blood cells and red blood cells to form chain inclusion bodies, due to the inclusion of inclusion bodies. The erythrocyte membrane makes the erythrocyte membrane stiff, susceptible to mechanical damage, and can not completely enter the blood circulation in the bone marrow, resulting in "ineffective hematopoiesis". Some red blood cells containing inclusion bodies mature and release to peripheral blood, but these red blood cells pass During microcirculation, it is easily destroyed, shortening its lifespan. In addition, the inclusion bodies of red blood cells also affect the permeability of red blood cells, further shortening their life span, leading to hemolytic anemia.
Anemia promotes the absorption of iron in the intestines (up to 80%), and the iron utilization disorder and repeated blood transfusion during the treatment process deposit a large amount of iron in the heart, liver, spleen, bone marrow and skin, leading to hemosiderin deposition. Symptoms, secondary hemochromatosis, myocardial and liver function damage, diabetes and other endocrine disorders.
Prevention
Pediatric beta thalassemia prevention
Actively carry out prenatal and postnatal work to reduce/control the inheritance of the thalassemia gene.
1. Premarital thalassemia screening to avoid marriage of patients with mild thalassemia can significantly reduce the chances of birth of heavy/intermediate thalassemia patients.
2. Promote prenatal diagnosis technology. For both parents or one of the thalassemia gene carriers, collect fetal villi, amniotic fluid cells or cord blood at 4 months of pregnancy, and obtain genomic DNA by polymerase chain reaction (PCR) technology for high-risk fetuses. For prenatal diagnosis, severe/intermediate children should terminate their pregnancy.
Complication
Pediatric beta thalassemia complications Complications jaundice edema anemia pneumonia fibrosis
Can be complicated by jaundice, hepatosplenomegaly, gallstone, can be complicated by hemolytic crisis, edema, ascites, anemia, bone changes, stagnant growth and development, often complicated by bronchial or pneumonia, complicated with hemosiderosis, causing organ damage, concurrent Heart failure, liver fibrosis, liver failure and so on.
Symptom
Symptoms of -thalassemia in children Common symptoms Hemosiderin, nasalgia, low liver function, liver fibrosis, loss of appetite, edema, heart failure
The child is asymptomatic at birth, more than the onset of infancy, 50% of the patients within 3 to 6 months after birth, occasionally the neonatal period, the earlier the onset of the disease, the heavier the condition, severe chronic progressive anemia Require blood transfusion to maintain life, 3 to 4 weeks of blood transfusion, with increasing age, with bone changes, first in the metacarpal bone, then to the long bones, ribs, and finally the skull, forming a special face (Downs face): head large The forehead is raised, the two ridges are slightly higher, the bridge of the nose is depressed, the eye distance is widened, the eyelids are edema, the skin is punctate, the appetite is weak, the growth and development are stagnant, the liver and spleen are swollen, and the spleen is obvious, up to the pelvic cavity. Often complicated by bronchitis or pneumonia, accompanied by hemosiderin, due to excessive iron deposition in the heart muscle and other organs such as liver, pancreas, etc., causing damage to the organ, the most serious of which is heart failure Hepatic fibrosis and liver failure are one of the important causes of death in children. If the disease is not treated, it will die more than 5 years old.
Examine
Pediatric beta thalassemia check
Blood picture
Hb 100120g/L, red blood cells<2.0×1012/L, red blood cell size varies, small cell hypochromic anemia, central light staining, peripheral blood smear red blood cell abnormal shape, visible pear shape, teardrop shape, small spherical , triangles, target shapes and fragments, basophilic red blood cells, polytropic red blood cells, increased nucleated red blood cells, increased reticulocytes (0.1), increased white blood cells and platelets, and hypersplenism.
2. Bone marrow
The nucleated red blood cell hyperplasia is extremely active, and the ratio of granule: red is inverted. In the middle, the young red blood cells are dominant, the cell body is small, the nucleus is pyknosis, and the cytoplasm is less blue. The methyl violet staining shows that the young red blood cells contain inclusion bodies (chain precipitation only ).
3. Red blood cell salt permeability test
The erythrocyte osmotic fragility is reduced, and 0.3% to 0.2% or less is completely hemolyzed.
4.HbF determination
This is an important basis for the diagnosis of severe -globin-producing anemia. HbF content is slightly elevated (<5%) or significantly increased (20% to 99.6%); HbA2 is often decreased, normal or moderately elevated, HbA2 3.5% ~8.0%.
5. Peptide chain analysis
High-performance liquid chromatography analysis can be used to determine the content of , , , peptide chains. When Cooley anemia, the / ratio is <0.1 (normal value is 1.0-1.1), because the disease is mostly point mutation, so PCR and ASO can be used to identify the mutation points. There are some differences in the -thalassemia gene mutations in different ethnic groups in China. The mutant genes of the southern Han nationality are CD41-42 (-TCTTT), CDL7 (AT), IVS-II-654 ( CT) and TATA-box28 (AG) are dominant, accounting for 85%-90%, and the double heterozygous mutation combination can reach nearly 100 species.
6. Other
The content of vitamin E in plasma and red blood cells decreased significantly, which was positively correlated with the condition; superoxide anion radical increased.
Regular X-ray, B-ultrasound, ECG and other checks.
X-ray examination of the bones, widening of the bone marrow cavity, thinning of the cortex and osteoporosis, thinning of the inner and outer plates of the skull, widening of the stenosis and formation of short hairy spurs.
Diagnosis
Diagnosis and diagnosis of -thalassemia in children
According to clinical manifestations and blood tests, especially HbF levels and family surveys can be diagnosed, conditional can be further used for peptide chain analysis or genetic diagnosis.
Differential diagnosis
1. Iron deficiency anemia: need to pay attention to the difference between severe iron deficiency anemia in infancy.
2. Hemoglobin E disease: HbE/ marine anemia syndrome is similar to this disease, but the former Hb electrophoresis shows HbE>30%.
3. The red blood cell G-6PD deficiency caused CNSHA severe and clinically similar to severe marine anemia, but the former infection and oxidative drugs can aggravate anemia, red blood cell Heinz body positive, HbF content can be identified.
