Thalassemia
Introduction
Introduction to thalassemia Thalassemia, also known as maritime anemia, is a group of hereditary small cell hemolytic anemia. A common feature is that one or more of the globin peptide chains in hemoglobin are reduced or not synthesized due to defects in the globin gene. Lead to changes in the composition of hemoglobin, the clinical symptoms of this group of diseases vary in severity, mostly manifested as chronic progressive hemolytic anemia. basic knowledge The proportion of illness: 0.005% Susceptible people: no specific people Mode of infection: non-infectious Complications: hypersplenism
Cause
Cause of thalassemia
Causes:
Protein gene deletion or point mutation:
The disease is caused by the deletion or point mutation of the globin gene. There are four kinds of peptide chains constituting globin, namely , , , chains, which are respectively encoded by their corresponding genes, and deletion or point mutation of these genes. It can cause the synthesis of various peptide chains, resulting in changes in the composition of hemoglobin. The thalassemia is usually divided into four types: , , and , among which and thalassemia are more common.
Beta thalassemia:
The human -globin gene cluster is located at 11p15.5, and the occurrence of thalassemia (referred to as -thalassaemia) is mainly due to point mutation of genes, a few gene deletions, gene deletions and some point mutations can completely inhibit the formation of -strands. It is called 0 thalassemia; some point mutations inhibit the production of the chain, which is called + thalassemia. There are more mutations in -thalassemia gene, and more than 100 mutation points have been discovered so far. 28 species have been found in China, of which 6 are common mutations: 1 41-42 (-TCTT), accounting for 45%; 2 IVS- II654 (C T), about 24%; 317 (A T); about 14%; 4TATA box - 28 (A T), about 9%; 5 71-72 (+A), about 2%; 6 26 ( G A ), that is, HbE26, accounting for about 2%.
Heavy beta thalassemia is homozygous for 0 or + thalassemia or double heterozygous for 0 and + thalassemia, because -strand formation is completely or almost completely inhibited, so that HbA synthesis with -chain is reduced or disappeared, and redundant The chain binds to the chain to become HbF( a2 2), which increases HbF significantly. Due to the high oxygen affinity of HbF, the patient's tissue is hypoxic, and the excess a chain is deposited in the young red blood cells and red blood cells to form a chain inclusion. The body attaches to the erythrocyte membrane to make it stiff, and is mostly destroyed in the bone marrow, resulting in "ineffective hematopoiesis". Some red blood cells containing inclusion bodies mature and are released into the peripheral blood, but they are easy when they pass through the microcirculation. It is destroyed; this inclusion body also affects the permeability of erythrocyte membrane, resulting in shortened life span of red blood cells. Due to the above reasons, the child is clinically chronic hemolytic anemia, anemia and hypoxia stimulate the secretion of erythropoietin Inducing bone marrow to increase hematopoiesis, thus causing bone changes, anemia increases the absorption of iron by the intestines, and repeated blood transfusions during the treatment process, causing iron to be stored in large quantities in tissues, resulting in Hemosiderin PAP.
Light thalassemia is a heterozygous state of 0 or + thalassemia. The synthesis of -strand is only slightly reduced, so its pathophysiological changes are extremely mild. Intermediate thalassemia is a double heterozygote and some + thalassemia. The homozygous variant of thalassemia, or the double heterozygote state of two different variant globin-producing anemia, has a pathophysiological change between heavy and light.
Alpha thalassemia:
The human a globin gene cluster is located at 16Pter-p13.3, and each chromosome has two a-bead genes. There are four a-globin genes in a pair of chromosomes. Most a-thalassemia (referred to as a thalassemia) is due to a. Due to the deletion of the globin gene, a small number of gene point mutations, if only one gene on a chromosome is missing or defective, the synthetic part of the alpha chain is inhibited, called a + thalassemia; if on each chromosome Both a genes are missing or defective, called a0 thalassemia.
Heavy alpha thalassemia is a homozygous state of a0 thalassemia, and its four a-globin genes are all deleted or defective, so that no a-chain is formed at all, so the synthesis of HhA, HbA2 and HbF containing a-chain is reduced, and the patient is in the fetus. A large number of gamma-chain synthesis 4 (Hb Barts) occurs, Hb Barts has a high affinity for oxygen, causing tissue hypoxia and causing fetal edema syndrome. Intermediate and alpha thalassemia are heterozygous for 0 and a + thalassemia. The state is caused by the deletion or defect of three a-globin genes. The patient can only synthesize a small amount of -chain, and the excess -chain is synthesized by HbH(4). HbH has high affinity for oxygen and is unstable. Hemoglobin is easily denatured and precipitated in red blood cells to form inclusion bodies, causing the erythrocyte membrane to be stiff and shortening the life of red blood cells.
Light alpha thalassemia is a+ homosexual homozygous or a0 thalassemia heterozygous state, it has only 2 a-globin gene deletions or defects, so there is a considerable amount of a-chain synthesis, pathophysiological changes are slight, static a thalassemia It is a heterozygous state of a+ thalassemia. It has only one alpha gene deletion or defect, the synthesis of a chain is slightly reduced, and the pathophysiological changes are very slight.
Prevention
Thalassemia prevention
1. Conducting population census and genetic counseling, making pre-marital guidance to avoid marriage between thalassemia gene carriers, and having important significance in preventing this disease. Genetic analysis is used for prenatal diagnosis, and heavy and can be used in early pregnancy. It is an effective method to prevent this disease by making a diagnosis of the thalassemia fetus and stopping the pregnancy in time to avoid the occurrence of fetal edema syndrome and the birth of patients with severe -thalassaemia.
2, the Mediterranean anemia belt due to the appearance, growth is no different from normal people.
3, vitamin supplements with ordinary people, when the doctor thinks it is necessary, because the appearance is not easy to detect the disease, often given iron tonic, should pay attention.
4, pre-marital check: the marriage target should be tested for the cause of the Mediterranean-type anemia, if it is, pay special attention to prenatal examination.
Complication
Thalassemia complications Complications, hypersplenism
1. Excess iron accumulation: Long-term blood transfusion will cause iron deposition and excessive iron accumulation will cause damage to multiple organs, mainly affected by heart, liver, pancreas and various endocrine organs. Patients will develop heart failure. , cirrhosis, liver function decline, diabetes, and short stature and hypoplasia due to multiple endocrine disorders.
2, the reaction caused by blood transfusion: common adverse reactions caused by blood transfusion include fever, chills and rash, etc., more serious reactions such as acute hemolysis, tracheal contraction and blood pressure drop, etc., although rare, but can not be ignored.
3. Diseases transmitted by blood transfusion: The main infections caused by blood transfusions are filtering viral diseases. Although in the whole process of blood transfusion, multiple preventive measures have reduced the chance of infection to a minimum. Occasionally, there are also infections due to blood transfusion. Examples of type and hepatitis B, as far as HIV infection is concerned, are extremely rare. Of the above three viruses, only hepatitis B can be prevented by effective vaccines.
4, the spleen is enlarged: under the stimulation of long-term anemia and hemolysis, many people with severe and medium-sized anemia will have a problem of spleen enlargement. Excessive spleen will aggravate anemia and cause patients to receive a larger amount of blood transfusion. More severe iron accumulation, timely removal of large spleen can often improve the situation.
5, the formation of gallstones: long-term hemolysis makes thalassemia patients more likely than ordinary people to suffer from gallstones, patients with gallstones may often appear right upper quadrant pain, skin, whitening yellow eyes and brown urine and other symptoms.
6. Side effects of iron removal: It is worth mentioning that iron tablets sometimes affect vision, hearing and bone growth. Therefore, the amount of iron-containing drugs should be determined according to the amount of iron accumulation. increase or decrease.
Symptom
Symptoms of thalassemia common symptoms osteoporosis hemosiderosis hepatosplenomegaly weakness
First, the symptoms:
Most of the disease occurs when the baby is sick, showing anemia, weakness, and abdomen ablation. Developmental delay, etc., heavy and long-growing dysplasia, often died before the age of adulthood. Light and intermediate patients can generally live to adulthood and can participate in labor. If you pay attention to diet and diet, you can reduce complications and improve symptoms. Insufficient endowment and weak kidney are the main reasons. The kidney is a congenital one, and the kidney is not full. Then biochemical passive. "Children's labor, get the mother's womb." It can be seen that '"Children's Labor" is closely related to parents. Kidney essence does not charge at the same time also affects the function and growth of the spleen and stomach of the day after tomorrow. The appearance of jaundice, accumulation, etc., has resulted in this false and misleading certificate.
Second, the signs:
In the severe beta thalassemia, X-ray examination of the bone showed a characteristic of chronic bone marrow hyperactivity. The cortical layers of the skull and long bones become thinner and the bone marrow cavity becomes wider. The space of the skull stenosis is obvious, and the trabecular trabeculae have a "sun ray"-like radiation pattern. Osteoporosis may occur in long bones. Cones and skulls may be in the form of particles or frosted glass. The finger (toe) bone loses its normal shape and is rectangular or even convex on both sides.
Examine
Thalassemia check
Laboratory inspection
(a). beta thalassemia
1. Heavy peripheral blood is small cell hypochromic anemia, red blood cell size varies, central light-stained area is enlarged, and abnormal shape appears. Target shape. Fragment red blood cells and nucleated red blood cells. Spotted red blood cells. Polychromatic red blood cells. Hao-week Small bodies, etc.; reticulocytes are normal or elevated. Bone marrow is markedly active in the red blood cell system, with moderate to late red blood cells, and mature red blood cells are the same as peripheral blood. Red blood cell osmotic fragility is significantly reduced. The HbF content is significantly increased, mostly >0.40, which is an important basis for the diagnosis of heavy thalassemia. The X-ray of the skull shows that the inner and outer plates of the skull are thinned, the barriers are widened, and vertical short-like spurs appear between the cortical bones.
2, light laboratory examination: mature red blood cells have mild morphological changes, red blood cell penetration brittle is better or lower, hemoglobin electrophoresis shows increased HbA2 content (0.035 ~ 0.060), which is the characteristics of this type. The HbF content is normal.
3, intermediate laboratory examination: peripheral blood and bone marrow changes such as heavy, red blood cell osmotic fragility reduced, HbF content is about 0.40 ~ 0.80, HbA2 content is normal or increased.
(two) alpha-thalassemia
1. The form of resting red blood cells is normal. The Hb Bart's content in cord blood at birth is 0.01-0.02, but disappears after 3 months.
2. The morphology of light red blood cells is slightly changed, such as different sizes, central light staining, and abnormal shape; the osmotic fragility of red cells is decreased; the denatured globin bodies are positive; the HbA2 and HbF contents are normal or slightly lower. The umbilical cord blood Hb Bart's content was 0.034 ~ 0.140, and disappeared completely at 6 months after birth.
3, the change of intermediate peripheral blood and bone marrow is similar to heavy thalassemia; red blood cell osmotic fragility is reduced; denatured globin is positive; HbA2 and HbF content is normal. At birth, the blood contains about 0.25Hb Bart's and a small amount of HbH; with age, HbH gradually replaces Hb Bart's, which is about 0.024 to 0.44. The inclusion body formation test was positive.
4, heavy peripheral blood mature red blood cell morphology changes such as heavy beta thalassemia, nucleated red blood cells and reticulocytes significantly increased. Almost all hemoglobin is Hb Bart's or a small amount of HbH, no HbA. HbA2 and HbF.
Diagnosis
Diagnosis of thalassemia
diagnosis:
According to clinical characteristics and laboratory tests, combined with a positive family history, a diagnosis can generally be made, and genetic diagnosis can be made when conditions permit.
Differential diagnosis
The disease must be identified with the following diseases.
1. Iron deficiency anemia The clinical manifestations of mild thalassemia and morphological changes of red blood cells are similar to those of iron deficiency anemia, so they are easily misdiagnosed, but iron deficiency anemia often has iron deficiency causes, serum ferritin content is reduced, bone marrow The extraneous iron granules are reduced, the red blood cells are free of original leaves, and the iron treatment is effective.
2, infectious hepatitis or cirrhosis due to HbH disease anemia is mild, accompanied by hepatosplenomegaly, jaundice, a small number of cases may also have liver damage, it is easy to be misdiagnosed as jaundice hepatitis or cirrhosis, but passed Medical history, family surveys, and red blood cell morphology observations can be identified by hemoglobin electrophoresis.
