Glucose-6-phosphate dehydrogenase deficiency in children
Introduction
Introduction to pediatric glucose-6-phosphate dehydrogenase deficiency Glucose-6-phosphatase dehydrogenase deficiency is a group of heterogeneous diseases caused by a significant deficiency of erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD). basic knowledge Sickness ratio: 0.0001% Susceptible people: children Mode of infection: non-infectious Complications: coma anemia
Cause
Pediatric glucose-6-phosphate dehydrogenase deficiency etiology
The incidence of this disease is quite complicated. For example, faba bean disease only occurs in G-6-PD deficiency, but not all G-6-PD deficiency patients have hemolysis after eating broad beans. Those who have developed faba bean disease eat broad beans every year, but not It must occur every year; the degree of hemolysis and anemia in the affected person is not parallel to the amount of broad bean eaten; the incidence of adults is significantly lower than that of children.
G-6-PD deficiency is X-linked incomplete dominant inheritance, and males have more outbreaks than females. Often the dominant inheritance is characterized by the fact that the disease-causing gene of either parent can be transmitted to the child as long as it is passed on to the child. Some individuals with dominant genetics may have no clinical manifestations, ie, the penetrance is not 100%, which is not fully dominant. That is to say, one parent may have a dominant gene carrier without clinical manifestation. Just like G-6-PD deficiency, because of X-linked, there is an appearance of incompleteness in the group, which is called X-linked incomplete dominant inheritance. Another possibility is genetic mutation, but this probability is extremely small.
Prevention
Prevention of glucosamine-6-phosphate dehydrogenase deficiency in children
The vast majority of this disease has incentives to induce acute hemolysis, so prevention is extremely important.
1. Group prevention: In areas with high incidence of G6PD, large-area census or pre-marital antenatal, prenatal, umbilical cord blood screening is a more effective and sensible method to detect G6PD deficiency.
2. Individual prevention:
(1) Removal of incentives On the basis of screening, a G6PD-deficient carrying card with banned or prudent use of drugs, food, etc. is issued for medical and personal reference.
(2) Neonatal jaundice: pregnant women with either couple or one of the G6PD deficiency, who take benzobarbital 0.03 to 0.06g per night for 2 to 4 weeks before delivery, can reduce neonatal hyperbilirubinemia or Reduce the incidence rate; take cord blood for routine screening during childbirth to find G6PD deficiency newborn; prenatal and infant refusal to use oxidative drugs or use camphor pills to store clothes, mothers avoid eating broad beans and their products, actively prevent neonatal infection.
Complication
Pediatric glucose-6-phosphate dehydrogenase deficiency complications Complications, coma, anemia
Hemolysis crisis may occur, severe cases may have oliguria, coma, convulsions, convulsions, dehydration, acidosis, etc., may be complicated by renal dysfunction, and even died of acute renal failure, often complicated by high bilirubinemia in the neonatal period Symptoms, progressive anemia, cholelithiasis, hepatosplenomegaly and so on.
Symptom
Pediatric glucose-6-phosphate dehydrogenase deficiency symptoms Common symptoms Huangqi appetite loss dizziness liver splenomegaly convulsions nausea dehydration abdominal pain proteinuria
Most of the red blood cell G-6-PD deficiency has no clinical manifestations. The clinical manifestations of hemolysis patients are similar to those of general hemolytic diseases. There are five types of hemolytic anemia caused by G-6-PD deficiency:
1. Congenital non-spherical erythrocyte hemolytic anemia (CN-SHA): chronic hemolysis can occur without cause, often in infants and young children, about half of cases in the neonatal period with hyperbilirubinemia Disease, severe cases are chronic hemolysis, with jaundice, anemia, splenomegaly three characteristics, light type usually mild anemia, no obvious jaundice, splenomegaly, hemolytic crisis every infection or drug-induced hemolysis, visible Increased red blood cells, red blood cell size and shape, with basophilic spots.
2. Fabies: During the harvest season of broad beans, it is the peak period of the disease, which occurs mostly in children. Mothers eat broad beans can cause babies to become ill by breastfeeding. The incidence is sharp, more than a few hours to several days after eating broad beans. Internal hemolysis, the main symptoms are burnout, dizziness, pale, fever, nausea, vomiting, abdominal pain, polydipsia, loss of appetite, jaundice, urine can be brown, red wine, blood red, soy sauce, etc., serious cases may be less Urine, coma, convulsions, convulsions, dehydration, acidosis, etc., half of the physical examination has liver, a small number of cases of splenomegaly, urine examination mostly hemoglobinuria, a small number of urinary bilirubin and urinary bilirubin increased, sometimes visible red blood cells, White blood cells and granules.
3. Neonatal hyperbilirubinemia due to G-6-PD deficiency in G-6-PD deficiency: G-6-PD deficiency is a neonatal area in areas with high G-6-PD deficiency The main cause of hyperbilirubinemia is jaundice within 3 days after birth. The peak of jaundice appears 4 to 7 days after birth, and the degree of jaundice is heavier. Generally, jaundice begins to subside 5 to 8 days after birth.
4. drug induced hemolysis (drug induced hemolysis): G-6-PD deficiency after taking oxidative drugs, can cause acute hemolysis, often 1 to 2 days after exposure to oxidative drugs, dizziness, headache, loss of appetite , nausea, vomiting, burnout, followed by fever, jaundice, abdominal pain, hemoglobinuria, urine color ranging from brown to soy sauce, at the same time, progressive anemia, varying degrees of anemia, reticulocytes normal or mild Increased, hepatosplenomegaly can also occur, a few severe cases can occur oliguria, no urine, with acidosis and acute renal failure and death, 10 to 40 days after stopping the drug, red blood cell destruction significantly slowed down, anemia gradually recovered, The main causes of hemolysis in patients with G-6-PD deficiency are:
(1) Antimalarial drugs: primaquine, malaria quinoline, penicillin and the like.
(2) Sulfonamides: sulfamethoxazole, sulfapyridine, p-aminobenzenesulfonamide, sulfacetamide, and the like.
(3) antipyretic analgesics: acetanilide, aminopyrine, phenylbutazone and the like.
(4) Furans: furantanidine, furazolidone, nitrofurazone and the like.
(5) Others: Thiazole sulfone, nalidixic acid, nitridazole, trinitrotoluene, naphthalene (camphor), methylene blue, chuanlian, toluidine blue, and the like.
5. Infectious hemolytic anemia: infection can also induce hemolytic episodes of G-6-PD deficiency, intravascular hemolysis occurs several days after infection, usually mild, but sometimes can cause severe hemolysis, Induction of hemolysis in patients with G-6-PD deficiency, common bacterial pneumonia, viral hepatitis and typhoid fever, and other influenza, infectious mononucleosis, leptospirosis, chickenpox, mumps, Bacterial dysentery, necrotizing enteritis, and Salmonella, Proteus, Escherichia coli, Streptococcus B, Mycobacterium tuberculosis and Rickettsia infection, G-6-PD deficiency, except for certain variants In addition to chronic hemolysis, most of the hemolysis occurs only under the influence of certain predisposing factors.
Examine
Examination of pediatric glucose-6-phosphate dehydrogenase deficiency
General laboratory tests for G-6-PD deficiency are non-specific compared to other hemolytic anemias. The diagnosis depends on the determination of erythrocyte G-6-PD enzyme activity, screening experiments and enzymes for G-6-PD deficiency. There are several methods for quantitative determination of activity.
1. Methmoglobin reduction test: The speed is significantly slower than that of normal people. This method is one of the commonly used tests for screening G-6-PD activity in China. The micro-histochemical elution method is suitable for heterozygotes. The reliability of the test is 75%. The disadvantage of this method is that if there is HbH, unstable hemoglobin, hyperlipidemia, macroglobulinemia and the like all cause false positive results.
2. Ascorbate-cyanide test: If G-6-PD is deficient, H202 destroys hemoglobin and forms a brown spot.
3. Nitrotetrazolium blue test: This test can be used to detect the amount of NADPH produced.
4. Fluorescent spot test: This test is the simplest, most reliable and most sensitive screening test.
5. G-6-PD activity assay: The amount of NADPH produced per unit time is used to reflect the activity of erythrocyte G-6-PD. The commonly used methods are the Zink Jam method recommended by the World Health Organization (WHO) and the International Hematology Standardization Committee (ICSH). The recommended Glock and Mclean methods, in the detection of erythrocyte G-6-PD activity, should pay attention to the clinical condition of the patient during the test, in the hemolysis period, aging, enzyme-deficient red blood cells are selectively removed in the peripheral blood, Young red blood cells are protected by high enzyme levels. The analysis of these cells can not truly reflect the G-6-PD activity of red blood cells. In order to solve this problem, it can be reviewed after 2 to 4 months of acute hemolysis, or Red blood cell G-6-PD activity was detected after centrifugation of the young red blood cells, but the use of precipitated red blood cells in the test system was not standard.
If the red blood cell infusion during the hemolysis episode also affects the G-6-PD activity measurement results, chronic non-spherical erythrocyte hemolytic anemia, no specific hematological changes, hemoglobin is generally 80 ~ 100g / L, reticulocyte count Increase to 4% to 35%, due to the increase in the proportion of reticulocytes, the average red blood cell volume is increased, the red blood cell half-life is significantly shortened, generally 2 to 17 days, the spleen of the defect-free cells is detained, so the spleen is generally ineffective, itself Hemolysis test has no diagnostic value. In some patients with severe G-6-PD deficiency, leukocyte function defects may occur due to leukocyte G-6-PD deficiency, mainly due to reduced phage activity, so the main clinical manifestations are peroxidase-positive bacteria. Repeated infection, neonatal jaundice, the serum total bilirubin concentration in most cases exceeds 273.6mol / L, and even as high as 684 ~ 8557mol / L, due to the severity of jaundice, can lead to a considerable part of children with bilirubin The incidence of encephalopathy is 10.5% to 15.4%. Patients with faba bean disease are classified according to the amount of hemoglobin:
(1) Heavy: hemoglobin is below 30g/L; hemoglobin is at 31-40g/L, and urinary occult blood is above +++ or without urine; or with serious complications such as pneumonia, heart failure, acidosis, mental disorders, Hemiplegia or binocular deviation in the same direction.
(2) medium: hemoglobin in 31 ~ 40g / L, urinary occult blood below ++; or hemoglobin 41 ~ 50g / L; or hemoglobin 51g / L or more, urinary occult blood ++++.
(3) Light type: hemoglobin 51g/L or more, urinary occult blood +++ or less.
(4) Concealed type: The number of hemoglobin and red blood cells is normal or slightly decreased. The Heinz body can be found in the peripheral blood. The patient will develop the disease after eating the broad bean. The same - the individual reacts to the broad bean at different times, obviously, except In addition to enzyme deficiency, there are other factors related to the disease. For example, Turrin et al found that there is macromolecular agglutination and protein cross-linking in the erythrocyte membrane during the hemolytic crisis induced by broad bean; membrane damage may be 10 times higher than that of red blood cells. It is related to the decrease of calcium-ATP activity. It is known that the two glycocalyx (fabaris and nucleus) in the broad bean are toxic components of broad bean. De Flora et al found that these two substances quickly inhibited the GSH production ability of defective red blood cells. , leading to metabolic disorders, routine chest X-ray, ECG and B-ultrasound, pay attention to the presence or absence of lung infection, can find gallstones, hepatosplenomegaly and so on.
Diagnosis
Diagnosis and differential diagnosis of glucose-6-phosphate dehydrogenase deficiency in children
According to the characteristics of acute hemolytic anemia, there is evidence of the history of eating faba beans within half a month or the history of taking suspicious drugs or infection within 2 days, and the causes of diabetes acidosis. If there is G-6-PD deficiency by screening test or enzyme activity, confirm.
Differential diagnosis
1. G-6-PD lacks drug-induced hemolytic anemia. Its clinical features and certain experimental features are similar to hemolytic anemia induced by unstable hemoglobin-related drugs and should be identified.
2. Other enzyme defects of hexose phosphate bypass, such as glutathione synthetase deficiency, and its clinical manifestations are similar to G-6-PD deficiency, and should be identified.
3. Exclusion of hemoglobin disease by heat instability test and hemoglobin electrophoresis, G-6-PD deficiency These two tests are normal, and some screening tests such as ascorbic acid (vitamin C) cyanide test hemoglobin can also be positive. However, the G-6-PD activity assay or the fluorescence spot assay is only positive for G-6-PD deficiency and can be identified accordingly.
