Pediatric X-linked severe combined immunodeficiency

Brief introduction of X-linked severe combined immunodeficiency disease in children Severe combined immunodeficiency (SCID) includes a group of hereditary diseases that may be associated with abnormal B cell differentiation or without abnormal B cell differentiation. If hematopoietic stem cell transplantation is not given, it often fails at an early age. The incidence of this disease is estimated to be 1 in 50,000 to 100,000 live births. basic knowledge The proportion of illness: this disease is rare, the incidence rate is about 0.0001% Susceptible people: infants and young children Mode of infection: non-infectious Complications: diarrhea, seborrheic dermatitis, hepatitis, pediatric sclerosing cholangitis, anemia

Pediatric X-linked severe combined immunodeficiency disease etiology

Congenital factors (98%):

XL-SCID is caused by mutation of the receptor chain (c) gene shared by IL-2, IL-4, IL-7, IL-9 and IL-15. The coding gene is located at Xq12~13.1, and c gene 8 has been found. There are 135 gene mutations in one exon, 5 of which are hotspots; the most common types of mutations are single base substitutions (missense mutations and nonsense mutations), followed by splicing site mutations, deletions and insertion mutations.

Other factors (2%):

Environmental factors lead to genetic mutations in the body's embryonic period.

Pathogenesis

c belongs to the cytokine receptor and is continuously expressed on T cells, B cells, NK cells, myeloid cells and erythroblasts. c and IL-2 receptor chain and chain together constitute a high affinity IL-2 receptor. The function of IL-2, the main function of tyrosine kinase Jak-3 is the signal transduction of c. The phenotype caused by Jak-3 deficiency is the same as that of XL-SCID. The single amino acid substitution of the extracellular domain of c protein blocks T cells. And the differentiation of NK cells, so far, the relationship between the phenotype and genotype of the disease has not been established.

Childhood X-linked severe combined immunodeficiency disease prevention

Pregnant woman health care

It is known that the occurrence of some immunodeficiency diseases is closely related to embryonic dysplasia. If pregnant women are exposed to radiation, receive certain chemical treatments or develop viral infections (especially rubella virus infections), they can damage the fetal immune system. Especially in the early pregnancy, it can affect multiple systems including the immune system. Therefore, it is very important to strengthen the health care of pregnant women, especially in the early pregnancy. Pregnant women should avoid receiving radiation, use some chemical drugs with caution, and inject rubella vaccine to prevent as much as possible. Virus infection, but also to strengthen the nutrition of pregnant women, timely treatment of some chronic diseases.

2. Genetic counseling and family survey

Although most diseases cannot determine the genetic pattern, genetic counseling for diseases with defined genetic patterns is valuable if genetically immunodeficiency in adults will provide the developmental risk of their children; if a child has autosomals Recessive genetic or sexually linked immunodeficiency disease, it is necessary to tell parents that their next child is likely to be sick, for patients with antibodies or complement deficiency patients should check the antibody and complement levels to determine the family disease For some diseases that can be genetically mapped, such as chronic granulomatosis, parents, siblings and their children should be genetically tested. If a patient is found, it should also be performed among his or her family members. Check that the child's child should be carefully observed at the beginning of the birth for any disease.

Children with X-linked severe combined immunodeficiency complications Complications, diarrhea, seborrheic dermatitis, hepatitis, pediatric sclerosing cholangitis, anemia

Repeated severe infection, persistent diarrhea; BCG and non-tuberculous mycobacterial infection can lead to the spread of fatal infection; can be complicated by seborrheic dermatitis, chronic deep ulcer; can cause chronic hepatitis, sclerosing cholangitis And chronic cirrhosis; gastrointestinal infections can be severe dyspepsia and cachexia, anemia can occur; chronic intracranial virus infection can be to chronic encephalopathy.

Symptoms of X-linked severe combined immunodeficiency syndrome in children Common symptoms Immunodeficiency diarrhea Gastrointestinal symptoms Granulocyte reduction Septicemia Digestive cachexia Thymus gland absent

1. Infection: The average age of diagnosis of XL-SCID is 5-6 months. The clinical manifestations are oral candidiasis, erythema, persistent diarrhea, respiratory syncytial virus, parainfluenza virus 3, adenovirus, Pneumocystis carinii Infections and Gram-negative septicemia, BCG-BCG and non-tuberculous mycobacterial infections can cause serious or fatal infections, and polio vaccination does not cause infection.

2. Skin manifestations: Seborrheic dermatitis can be very serious, can be confused with graft-versus-host disease, ectodermal dysplasia has also been reported, chronic deep ulcers can occur in the buccal mucosa, tongue and perineum.

3. Gastrointestinal symptoms: including chronic hepatitis caused by cytomegalovirus or other pathogens, involving the bile duct can lead to sclerosing cholangitis and chronic cirrhosis, can be complicated by rotavirus, Giardia or Cryptosporidium infection, resulting in Severe dyspepsia and cachexia.

4. Abnormal blood system: including neutropenia, red blood cell hypoplasia, large cell anemia resistant to vitamin B12 and folic acid, eosinophils and mononuclear cells suggest an uncommon infection such as Pneumocystis carinii infection.

5. Neurological manifestations: Chronic progressive multifocal leukoencephalitis caused by chronic encephalopathy such as Jamestown and Canyon virus can occur.

Examination of children with X-linked severe combined immunodeficiency disease

Lymphopenia (CD3 / CD4 or CD3 / CD8 cells), proliferative response and NK cells disappear, B cell number is often normal, but B cell function is seriously impaired, 3 Ig concentrations are low, or even absent, confirm c gene mutation The XL-SCID can be diagnosed.

Routine chest X-ray, B-ultrasound, EEG and brain CT examination.

Diagnosis and differential diagnosis of X-linked severe combined immunodeficiency disease in children

diagnosis

According to the clinical manifestations of repeated severe infection within 6 months, the number of T, B cells and serum immunoglobulin decreased, the cellular immunity and humoral immune function were significantly lower, X-ray examination of thymus deficiency, lymphoid pathology examination of plasma cells, Lymphopenia can diagnose this disease.

Differential diagnosis

1. Reticular dysgenesis: This disease is very rare, not only the defect of lymphoid cell differentiation but also the differentiation of myeloid cells, which may be a hematopoietic disorder, because it can be treated by bone marrow transplantation; it can be associated with multiple gastrointestinal tracts. Blocking, considered for indirect recessive inheritance.

2. Autosomal recessive SCID alymphocytosis About 20% of SCID patients are characterized by a common deficiency of T and B lymphocytes, while functional NK cells can be measured. Autosomal recessive inheritance.

3. Autosomal recessive SCID: This type is also T(-)B(), accounting for about 10% of SCID. The differentiation of NK cells exists in this disease. After bone marrow transplantation, the function of host lymphocytes is completely restored.

4. Adenosine deaminase deficiency (ADA deficiency): Adenosine deaminase (ADA) is an enzyme in the purine metabolic pathway that catalyzes the conversion of adenosine to inosine and deoxyadenosine (dAdo) into deoxygenated muscle. Glycoside, when the ADA is deficient, the above catalysis is blocked, dAdo can diffuse freely, and is phosphorylated to become deoxyadenosine triphosphate (dATP), which inhibits ribonucleotide reductase, thereby suppressing cell differentiation, and adenosine and dAdo are blocked. Sulfur-adenosine homocysteine hydrolase, which makes adenosine homocysteine unable to confer methylation to DNA, due to adenosine, dAdo and dATP accumulating in lymphocytes, especially in developing T cells, Infect the cells.

In most (about 85%) ADA-deficient patients, both T and B cell counts are low, and clinical signs appear earlier. In addition to severe infection and growth and developmental disorders, nearly 50% of patients develop skeletal abnormalities, including rib cartilage junctions. Cup shape and separation, as well as mild pelvic dysplasia, some patients also have neurological symptoms, including cortical blindness and low muscle tone, in addition, basement membrane sclerosis and renal dysfunction, early cases, dATP values in compressed RBC > 1000ng/ml, late case <1000ng/ml, some ADA defects have no immunodeficiency, dATP is normal or marginal.

The ADA gene is located at 20q13-ter, including 1089 nucleotides, and is divided into 12 exons. Four different loci, 14 variants and 5 break variants have been found.

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