Pediatric hereditary ellipsocytosis

Introduction to pediatric hereditary elliptic polycythemia Hereditary elliptic polycythemia (HE) is another erythrocyte membrane defect hemolytic anemia. The disease is characterized by a large number of oval mature red blood cells visible in the surrounding blood. The clinical symptoms vary in severity, and the most severe ones can die in the uterus due to fetal edema. A small number of oval red blood cells can also be seen in normal human blood, generally no more than 15%. This disease has more than 25% of red blood cells. According to the degree of hemolysis, there are three types: no hemolysis (hidden type), mild hemolysis (hemolysis compensatory type), and obvious hemolysis acceleration type. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: jaundice cholelithiasis

Pediatric hereditary elliptic polycytosis etiology

(1) Causes of the disease

Molecular genetic abnormalities that cause membrane defects in this disease include: membrane contractile protein alpha chain gene abnormality (called HE mutation), membrane contractile protein alpha chain low expression allele (called LE, including LELY, other LE, chain gene Absence, etc.), membrane contractile protein chain gene abnormality, 4.1 protein abnormality and blood group glycoprotein C and D (D is a variant of C) lack, mainly due to structural abnormality of membrane contractile protein, a small number of 4.1 protein deficiency of erythrocyte membrane Or a defect in the binding of the 3 protein to the ankyrin.

(two) pathogenesis

Abnormal membrane shrinkage protein genes (mainly HE mutations) cause membrane contractile proteins to replace normal tetramers with dimers, resulting in decreased cell membrane stability, and the ability of -lelag alleles to express -chain deficiency and -chain binding. However, it has no obvious effect on the production of normal membrane contractile protein; if there is a mutation of chain gene at the same time, obvious elliptical erythrocyte changes may occur, and the membrane protein abnormality mainly decreases the membrane stability by affecting the horizontal interaction of the membrane skeleton. 4.1 Protein dysfunction is caused by mutation of 4.1 protein gene, which makes the protein shorter and thus incomplete. The normal function of 4.1 protein is to strengthen the binding of membrane contractile protein to actin. Therefore, its abnormality can affect the stability of membrane skeleton. 4.1 The degree of protein deficiency is related to the decrease of cell deformability and the increase of mechanical fragility. The mechanism of HE forming oval red blood cells is not fully understood. Normal red blood cells can form oval cells during aging. HE red blood cells are only released into the blood circulation. After the formation of an ellipse, nucleated red blood cells and reticulocytes are normal, speculated When the red blood cells are subjected to a certain shearing force after microcirculation, the membrane skeleton proteins are reconnected, and the red blood cells become elliptical. When the external force is removed, they cannot return to normal and become permanent elliptical cells.

It has been confirmed that the abnormality of the above membrane skeleton protein can cause the horizontal junction defect of the erythrocyte membrane skeletal protein, and the stability of the membrane skeleton is weakened, which is closely related to the formation of ellipsoidal red blood cells, and the red blood cells are easily broken under the action of external force, so the disease is more serious. The more heterogeneous cells and broken cells, the severity of hemolysis is related to the proportion of membrane contractile protein dimer. More than 40% to 50% often have severe hemolysis, requiring splenectomy; and the amount of dimer depends on the amount of dimer. At the mutation site, as well as the content of the membrane-shrinking protein in the membrane, the increase in membrane mechanical brittleness is related to the increase in the content of dimers that do not form tetramers, while the erythrocyte deformability is related to the amount of membrane-shrinking protein, most ovals. The spleen is destroyed in the spleen and a small part is destroyed in the liver and bone marrow.

Pediatric hereditary erythrocytosis prevention

The disease is an autosomal dominant hereditary disease and should be passed from pre-pregnancy to prenatal: pre-marital physical examination plays a positive role in preventing birth defects. The size of the effect depends on the examination items and contents, including serological tests (such as hepatitis B virus, Treponema pallidum, HIV), reproductive system tests (such as screening for cervical inflammation), general physical examination (such as blood pressure, electrocardiogram), and asking about family history of the disease, personal medical history, etc., doing genetic disease counseling, pregnant women avoiding harmful factors as much as possible Including away from smoke, alcohol, drugs, radiation, pesticides, noise, volatile harmful gases, toxic and harmful heavy metals, etc., in the process of antenatal care during pregnancy, systematic screening of birth defects, including regular ultrasound examination, serum Study screening, etc., if necessary, also carry out chromosome examinations. Once an abnormal result occurs, it is necessary to determine whether it is treatable, how to prognose, etc., and take practical measures for diagnosis and treatment.

Pediatric hereditary erythrocytosis complications Complications jaundice cholelithiasis

There are varying degrees of jaundice and hepatosplenomegaly, long-term hemolysis can be complicated by cholelithiasis, and some patients with severe hemolysis can be complicated by aplastic anemia or hemolytic crisis.

Pediatric hereditary elliptic polycythemia symptoms common symptoms erythrocytosis red blood cell life shortens bilirubin increased hemolysis

HE is an autosomal dominant hereditary hemolytic disease. According to clinical manifestations, red blood cell morphology and family surveys, the vast majority of HE can be clearly diagnosed. Its clinical manifestations and hematological changes vary widely. The main diagnosis of HE is red blood cell morphology. The most important feature is that the oval blood cells in the peripheral blood are more than 25%, generally 60% to 90%, and the rod cells can exceed 10%. A positive family history is helpful for diagnosis. If there is no positive family history, and oval blood cells in the peripheral blood are greater than 50%, it can generally be diagnosed. If there is no family history and the oval red blood cells are not enough, the other blood system diseases should be excluded. Oval cells can also be found in some normal people, but the number is rarely more than 15%, generally less than 5%, and rod cells are rare.

(1) At present, there are three types of domestically based hemolysis:

1. No hemolysis (hidden type): Although oval red blood cells increase, there is no hemolysis.

2. Mild hemolysis (hemolysis compensatory type): Red blood cell life is slightly shorter than normal, reticulocytes are slightly increased, and haptoglobin is lower than normal. Due to the compensatory hematopoietic function, anemia does not occur. The vast majority of patients fall into this category.

3. Hemolysis is obviously accelerated: the life span of red blood cells is shortened, the reticulocytes are obviously increased, and the clinical symptoms and hereditary spherocytosis are difficult to distinguish. This type accounts for only about 12% of all cases. Severe hyperbilirubinemia can occur in the neonatal period and even need to be exchanged for treatment. There is a risk of bone marrow non-proliferation in the case of co-infection, and there are reports of cholelithiasis.

(2) Since there is no clear correlation between clinical manifestations and molecular lesions, the disease is currently classified into 5 types according to clinical manifestations and laboratory tests, ie common type (light) HE, heavy HE, hereditary pyropoikilocytosis (HPP), globular cellular HE, and oral cellular HE.

Examination of pediatric hereditary elliptic polycythemia

1. Red blood cell morphology: oval, oval, cigar-shaped or sausage-shaped mature red blood cells in the peripheral blood (Figure 1), greater than 25%, this abnormal shape may not exist at birth, more than 4 after birth At 6 months, MCHC is normal. In addition, in spherical globular HE, there are small spherical red blood cells and small oval cells. In oral HE, there are many cell membranes with stiff cell membranes, and the central light-stained area has a rod-like structure. When it is severely divided, spherical cells or red blood cell fragments may appear in the surrounding blood, and the reticulocytes and nucleated red blood cells are normal.

2. Erythrocyte fragility test: Normal type HE is mostly normal, and it is increased in children with spherical cell HE and severe HE. The fragility test and autolysis test after incubation are slightly increased, and can be corrected after adding glucose or ATP.

3. Red blood cell autolysis test: In the spherical cell HE increased, the addition of glucose or ATP only partially corrected, the red blood cell deformability of each type of HE was reduced, 51Cr labeled red blood cells showed a significantly shortened lifespan, mostly destroyed in the spleen, in HPP, red blood cells Sensitive to heat (45 to 46 ° C is broken, normal red blood cells are broken at 49 ° C).

4. Molecular biological analysis of erythrocyte membrane proteins and their genes: SDS-PAGE analysis can be used to detect abnormalities of HE erythrocyte membrane proteins. SDS-PAGE combined with other methods can quantitatively analyze membrane protein components, using low ionic strength non-denaturing gels. Electrophoretic analysis can detect the ratio of membrane contractile protein dimers and tetramers in the erythrocyte membrane skeleton, and molecular genetic methods can be used to detect membrane protein gene mutations.

5. Regular imaging examination, such as chest X-ray, B-ultrasound, pay attention to the presence or absence of lung infection, gallstone and hepatosplenomegaly.

Diagnosis and diagnosis of hereditary elliptic polycythemia in children

diagnosis

According to clinical manifestations, red blood cell morphology and family survey, the vast majority of HE can be clearly diagnosed. The main diagnostic basis of HE is red blood cell morphology. The vast majority of HE peripheral blood oval red blood cells are more than 25%, generally up to 60%-90. %, rod cells can be more than 10%, a positive family history is helpful for diagnosis. If there is no positive family history, and the oval blood cells in the peripheral blood are more than 50%, it can be diagnosed. There is no family history and the oval red blood cells are not enough. Many people need to rule out other hematological diseases. Oval cells can also be found in some normal people, but the number is rarely more than 15%, generally less than 5%, and rod cells are rare.

Differential diagnosis

The disease should be associated with globin-producing anemia, such as thalassemia, iron deficiency anemia, megaloblastic anemia, myelofibrosis, myelodysplastic syndrome and pyruvate kinase deficiency, etc., may be accompanied by a small number of oval red blood cells In addition to oval red blood cells, the above-mentioned diseases often have other special atypical cells and clinical signs. The proportion of oval red blood cells in these diseases is generally <50%, but the proportion of elliptical red blood cells is low due to a small part of HE. Therefore, it is not possible to diagnose according to this, and it is more important to differentiate the family history of diagnosis.

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