unstable hemoglobinopathies
Introduction
Introduction to unstable hemoglobinopathy Unstable hemoglobin disease is caused by a change in the amino acid composition of the or globin chain, resulting in unstable hemoglobin molecular structure, denaturation and precipitation, and formation of red blood cell denatured globin bodies (Heinz bodies), called unstable hemoglobin. basic knowledge The proportion of illness: has a genetic predisposition, the incidence rate is about 0.001% - 0.005% Susceptible people: no specific people Mode of infection: non-infectious Complications: cholelithiasis
Cause
Causes of unstable hemoglobinopathy
(1) Causes of the disease
Mutation of -globin gene or -globin gene leads to changes in the amino acid composition of the corresponding globin chain. In some patients, the mutant gene inherits from the parents and exhibits autosomal dominant inheritance; some patients have no positive family history, and the genetic mutation may be Spontaneous somatic gene mutations, all cases found so far are heterozygous, no homozygous patients have been found, occasionally double heterozygous patients, which may be related to this disease is rare, may also be related to the difficulty of survival of homozygotes.
(two) pathogenesis
The amino acid composition and order of the globin chains play a decisive role in maintaining the structure and function of hemoglobin. Substitution, insertion or deletion of globin chain amino acids can alter the structure and function of hemoglobin, and the following changes are known to cause unstable hemoglobin. produce:
1 amino acid combined with heme is replaced, making hemoglobin easy to lose, such as Hb Hammersmith;
2 non-polar amino acids are replaced by polar amino acids, changing the hemoglobin configuration, such as Hb Bristol;
3 amino acid substitution occurs at the contact between the 1 chain and the 1 chain, causing instability of the globin chain, such as Hb Philly;
4 amino acid substitution occurs in the third position of the alpha helix, making the spiral easy to break, such as Hb Duaree;
5 amino acid substitution occurs at the and helix contacts, affecting the binding of heme to the globin chain, such as Hb Sayannah;
The deletion or insertion of 6 amino acids occurs at the position of the alpha helix, which makes hemoglobin easily dissociated from the globin chain. For example, Hb Neteroi, the above various changes can make hemoglobin unstable and precipitate, forming denaturation in red blood cells. The globin body attaches to the erythrocyte membrane, which reduces the deformability of the membrane, becomes stiff, and eventually breaks down in the microcirculation, especially in the spleen.
Prevention
Unstable hemoglobin disease prevention
Unstable hemoglobinopathy is an Hb in which the molecular structure is unstable due to a mutation or substitution of an amino acid in the alpha or beta chain due to a mutation in the globin gene in the hemoglobin molecule. At present, more than 130 types of unstable hemoglobin have been found, and most of them, except for a few, have different hemolytic anemias. The alpha-chain polymer in beta thalassemia, HbH (4) and HbBart's (4) in alpha thalassemia, is also unstable hemoglobin.
Complication
Unstable hemoglobin disease complications Complications cholelithiasis
Cholelithiasis, infection, and acute hemolytic crisis are the most common complications of this disease and should be treated as soon as possible.
Symptom
Symptoms of unstable hemoglobin disease Common symptoms Hair hemolytic anemia
There are more than one hundred kinds of unstable hemoglobin, and the clinical manifestations caused by different unstable hemoglobin are very different. Most patients with unstable hemoglobin do not have anemia due to compensatory hyperplasia of bone marrow erythroid, or only mild hemolytic anemia. However, when an infection or oxidant is taken, the unstable hemoglobin precipitation is aggravated, the hemolytic anemia is aggravated, and the patient often has a clear diagnosis because of the medical treatment. The gamma-chain abnormality patient may have hemolytic anemia at birth, and then the -chain is gradually normalized. After -chain substitution, hemolytic anemia gradually disappeared after 6 months. Patients with abnormal -chain were normal at birth, and then -chain was gradually replaced by abnormal -chain. Chronic hemolytic anemia appeared after 0.5 to 1 year old, and a few unstable hemoglobins (such as HbDuaree) has higher oxygen affinity than normal, and reduces oxygen release to tissues, causing hemoglobin concentration to rise to the upper limit of normal hemoglobin concentration or slightly higher than normal. In addition to anemia, patients may also have jaundice, splenomegaly, if unstable hemoglobin is oxidized When methemoglobin is formed, cyanosis occurs.
Examine
Examination of unstable hemoglobinopathy
1. Peripheral blood hemoglobin is normal or decreased, red blood cells are hypochromic, uneven size, visible multi-stain, basophilic red blood cells, reticulocyte increase may not be parallel with anemia, especially when unstable hemoglobin oxygen affinity is increased, There can be no anemia and the reticulocyte count is increased.
2. Thermal denaturation test, isopropanol test and acetaminophen test The thermal denaturation test is easy to have a false positive. It needs to be a normal control. Isopropanol not only precipitates unstable hemoglobin, but also precipitates HbF. It should be identified with 0.1. % acetophenone and incubation at 37 ° C for 2 ~ 4h can induce the formation of denatured globin bodies, and the denaturing globin bodies are easily seen in the peripheral hemoglobin of patients after spleen removal.
3. Hemoglobin electrophoresis has limited effect on the identification of unstable hemoglobin, as most unstable hemoglobin migrates at a different rate than normal hemoglobin.
4. Oxygen dissociation curve examination can find out whether the oxygen affinity of unstable hemoglobin is abnormal.
According to the condition, clinical manifestations, symptoms, signs, choose to do ECG, B-ultrasound, X-ray, biochemical examination.
Diagnosis
Diagnosis and diagnosis of unstable hemoglobin disease
For patients with unexplained congenital non-spherical hemolytic anemia, the possibility of the disease should be considered. The main basis for diagnosis is to prove the existence of unstable hemoglobin. If the oxygen affinity of hemoglobin is abnormal, it is also valuable for diagnosis. The patient has a positive family history. After the diagnosis of unstable hemoglobin disease, if you want to understand the abnormal existence of unstable hemoglobin, you need to analyze the amino acid composition of the globin chain.
