Pediatric Congenital Leukocyte Dysgranulocytosis Syndrome
Introduction
Introduction to congenital leukocyte granule abnormality syndrome in children Chédiak-Higashisyndrome (Chédiak-Higashisyndrome), also known as Chédiak-Higashi syndrome, Chédiak-Higashi-Steinbrinck syndrome, hereditary leukocyte granule syndrome, congenital peroxidase granules, abnormal whitening of congenital white blood cells Syndrome (congenitalleukocyticabnormalyalbinismsyndrome) and the like. It is a rare albino disease with abnormal nervous system and blood system. It is an autosomal recessive hereditary disease, which is more common in the offspring of close relatives. basic knowledge The proportion of illness: 0.002% Susceptible people: children Mode of infection: non-infectious Complications: hypersplenism hemolytic anemia
Cause
Causes of congenital leukocyte granule abnormality syndrome in children
Genetic (55%):
Autosomal recessive hereditary diseases are more common in offspring of close relatives, caused by mutations in the human CHS1 gene.
The pathogenesis of this disease may be a widespread abnormality in the cell membrane boundary of granulocytes. Abnormal granulocyte chemotaxis may be related to large particles in the cell membrane or cytoplasm, causing disorder through micropores and poor response to chemotactic stimulating factors. Leukocyte abnormality in the electron microscopic leukocyte chemical structure, there are huge lysozyme granules, acid hydrolase, phospholipase, peroxidase, etc., and abnormal lysozyme particles are bound to the lysosomal membrane, so it is considered Is a lysosomal disease, because a variety of hydrolases can not be released into the phagocytic vacuoles due to lysosomal membrane defects, degranulation is also delayed, the result of this neutrophil is characterized by weakened chemotaxis, killing Poor bacterial ability, easy to destroy in the spinal cord and cause neutropenia.
Prevention
Prevention of congenital leukocyte particle abnormality syndrome in children
With reference to the prevention of congenital diseases, preventive measures should be carried out from pre-pregnancy to prenatal:
Pre-marital medical examination plays an active role in preventing birth defects. The size of the effect depends on the examination items and contents, including serological examination (such as hepatitis B virus, treponema pallidum, HIV) and reproductive system examination (such as screening for cervical inflammation). General medical examinations (such as blood pressure, electrocardiogram) and asking about the family history of the disease, personal medical history, etc., do a good job in genetic disease counseling.
Pregnant women should avoid harmful factors as far 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 is required, including Regular ultrasound examination, serological screening, etc., if necessary, a chromosome examination.
Once an abnormal result occurs, it is necessary to determine whether to terminate the pregnancy; the safety of the fetus in the uterus; whether there is sequelae after birth, whether it can be treated, how to prognose, etc., and take practical measures for diagnosis and treatment.
The prenatal diagnostic techniques used are:
1 amniocytes culture and related biochemical examination (amniotic puncturing time is 16 to 20 weeks of pregnancy is appropriate);
2 pregnant women blood and amniotic fluid alpha fetoprotein determination;
3 ultrasound imaging (applicable in about 4 months of pregnancy);
4X line examination (after 5 months of pregnancy) is beneficial for the diagnosis of fetal skeletal deformities;
5 Determination of sex chromatin in villus cells (40 to 70 days of conception), predicting fetal gender to help diagnose X-linked genetic diseases;
6 application gene linkage analysis;
7 fetal mirror examination.
Through the application of the above technology, the birth of a fetus with severe genetic diseases and congenital malformations is prevented.
Complication
Complications of congenital leukocyte granule syndrome in children Complications, hypersplenism, hemolytic anemia
Liver and spleen and lymph nodes, hypersplenism and hemolytic anemia, easy to infection, especially skin, respiratory staphylococci and other Gram-positive bacteria infection, and can develop progressive neutropenia, anemia, Thrombocytopenia.
Symptom
Symptoms of Congenital Leukocyte Granule Syndrome in Children Common Symptoms Bacterial Infections Nasal Bleeding Photophobia Disorders Liver Splenomegaly Lymph node enlargement Skin is metallic color... Thrombocytopenia neutropenia light reflection disappears
Both of these symptoms can be affected, and the parents of the children are mostly close relatives. The clinical manifestations are as follows.
1. Skin symptoms: It is more special, it can appear in infancy, the skin is partially whitened, the exposed parts are slate-like gray or black, and the hair is linen or dark brown, all of which are silver, especially in the sun or After washing.
2. Ocular symptoms: It is more complicated and can present ocular albinism. The iris pigmentation is blue-violet or brown, translucent, the fundus pigment disappears, the retina is gray, and horizontal nystagmus is visible in the light.
3. Liver and spleen and lymphadenopathy: About 85% of patients have liver and spleen and systemic lymphadenopathy. Some people call it "lymphoma", which may be an increase in the reactivity of lymphoid cells. When the spleen is obvious, hypersplenism may occur. Hemolytic anemia.
4. susceptible to infection: especially skin, respiratory infections of staphylococci and other Gram-positive bacteria.
5. Nervous system symptoms: may have cerebellar tremor, poor distance, neck muscle tension, paralysis, ptosis, pupils are not large, light reflex disappears, coma, cerebrospinal fluid protein and cell number increase, EEG abnormal, surrounding Neuropathy and so on.
6. Hematological features: There are Döhle small body of toluidine particles in the cytoplasm of leukocytes. The granulocytes are swollen, degeneration and lobulation are not obvious. The pulp lacks normal neutral particles, but contains 1 to 6 or A variety of round, oval, 1 ~ 2m diameter stained purple gray blue abnormal particles, neutrophils can be seen 1 to 6 abnormally large particles, a transparent band is visible around.
Root 1972 proved that children with good phagocytic function, but the bactericidal activity is defective, prone to infection, and can progress to progressive neutropenia, can have anemia, thrombocytopenia.
Examine
Examination of congenital leukocyte granule abnormality syndrome in children
1. Blood and bone marrow examination: Progressive neutropenia, progressive anemia, decreased hemoglobin, decreased red blood cell count, thrombocytopenia, neutrophils (including early and middle-aged acidophilus, basophils) The cytoplasm contains peroxidase-positive particles and azure Dohle small body-like particles of different sizes, ranging from 2 to 5 m in diameter. This granule is also found in lymphoid and monocytes, and vacuoles in bone marrow cells are occasionally swallowed. Foreign bodies, some nucleus are more pyknotic, cellular immunity, immunoglobulin and complement are normal.
2. Cerebrospinal fluid examination: The number of proteins and cells increases.
3. Pathological examination: Large lysosome-like particles can be seen in many tissues throughout the body.
4. Deficiency of neutrophil function: Invasive and chemotactic insufficiency, low bactericidal power, normal phagocytosis.
5. Determination of neutrophil cyclic nucleotides: cAMP content was significantly increased (7-8 times that of normal people), and cGMP content was decreased.
6. Increased serum lysozyme content: Because neutrophils are easily destroyed, serum lysozyme activity is increased.
7. Hair examination: Large melanin particles can be found in the hair under the microscope.
8. X-ray chest X-ray, B-ultrasound examination, found liver, splenomegaly, large mediastinum, EEG examination showed abnormal brain waves.
Diagnosis
Diagnosis and diagnosis of congenital leukocyte particle abnormality syndrome in children
diagnosis
According to the skin, hair, eye pigmentation, nystagmus, photophobia, visual impairment and other eye symptoms, as well as special appearance and hematological characteristics can be diagnosed, children with one or more of the following abnormalities should suspect this The possibility of illness:
1. Repeat unexplained bacterial infections.
2. Hair, skin, pigmentation of the fundus.
3. Large peroxidase-positive lysosome particles appear in granulocytes of peripheral blood or bone marrow.
4. Light, moderate neutropenia.
5. Although the platelet count is normal, it is easy to bruise or nosebleeds.
6. Unexplained hepatosplenomegaly (related to accelerated disease).
The disease is often manifested in infants and young children, but also diagnosed at a later accelerated phase. The diagnosis requires the discovery of large lysosomal particles in peripheral blood or bone marrow granulocytes. Some patients have extensive destruction of the granulocyte precursor cells in the bone marrow. There are few peripheral blood granulocytes, which requires bone marrow aspiration.
Differential diagnosis
Identification of diseases associated with liver, spleen, and lymphadenopathy. The above clinical features and laboratory features are helpful for identification. Differential diagnosis includes some albinism in other genetic forms, such as Griscelli syndrome, Hermansky-Pudlak syndrome, Griscelli syndrome. The neutrophils lack large cytoplasmic granules, large patches of pigmentation can be found in the hair shaft, and mature melanosomes can be seen in melanocytes. Children often develop deadly lymphoid histiocytic syndrome before the age of 10, and CHS. Similar to the accelerated phase, Hermansky-Pudlak syndrome is characterized by platelet dysfunction and associated bleeding quality. In addition, large particles resembling CHS cells can be found in acute, chronic myeloid leukemia cells.
