Adenosine deaminase deficiency in children

Introduction to adenosine deaminase deficiency in children Deficiency of adenosine deaminase in children is an autosomal recessive disorder. Deficiency of adenosine deaminase (ADA) leads to accumulation of the nucleotide metabolite dATP, which arrests early T cells and B cells in the pro-T/pro-B phase, leading to defects in T cells and B cells. . basic knowledge The proportion of illness: 0.002% Susceptible people: children Mode of infection: non-infectious Complications: diarrhea pneumonia otitis media meningitis neurological deafness

Deficiency of adenosine deaminase in children

(1) Causes of the disease

ADA is an aminohydrolase involved in the process of purine metabolism, which catalyzes the deamination of adenine nucleosides to inosine. Inosine is converted to hypoxanthine by the action of purine nucleoside phosphorylase (PNP). The yellow ostrich phosphoribosyltransferase (HGPRT) is converted to phosphoinosine or converted to uric acid excretion. The gene encoding ADA is located on the long arm of chromosome 20, and the majority of children with ADA mutations are only CpG dinucleotide CT. Point mutations, the entire gene or part of the gene deletion is only found in a few cases.

(two) pathogenesis

ADA lacks the accumulation of damaged toxic intermediate metabolites such as deoxyadenosine and adenosine triphosphate in patients with lymphocytes, which can dissolve T cells and B cells within 4 days, the degree of residual ADA activity and the severity of its clinical manifestations, and deoxyadenosine and adenosine triphosphate The accumulation of toxic intermediate metabolites is inversely proportional. Although all cells have ADA and PNP, the concentration of different cells varies greatly. The two enzyme defects mainly affect lymphocytes. Deoxyadenosine mainly comes from fast-metabolizing cells. The breakdown of cells and lymphocytes, adenosine triphosphate (ATP) and cell death are the main sources of adenosine.

Prevention of adenosine deaminase deficiency in children

1. Maternal 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 have viral infections (especially rubella virus infection), they can damage the fetus. The immune system, especially in the first trimester, can involve multiple systems including the immune system. Therefore, it is important to strengthen maternal health care, especially in early pregnancy. Pregnant women should avoid radiation, use some chemical drugs with caution, and inject rubella vaccine. As far as possible to prevent viral infections, but also to strengthen the nutrition of pregnant women, timely treatment of some chronic diseases.

2. Genetic counseling and family surveys Although most diseases cannot determine the genetic pattern, it is valuable to conduct genetic counseling for diseases in which genetic patterns have been identified. If adults have hereditary immunodeficiency diseases, they will provide the developmental risks of their children; If a child has an autosomal recessive or sexually linked immunodeficiency disease, tell parents that they are more likely to have a disease in their next child. For immediate family members of patients with antibodies or complement deficiency, antibodies and complement should be examined. Level to determine the family's disease pattern. For some diseases that can be genetically mapped, such as chronic granulomatosis, parents, siblings and their children should be tested for localization. If a patient is found, it should be in him. The family members of her) are examined and the child's children should be carefully observed at the beginning of their birth for any disease.

Deficiency of adenosine deaminase in children Complications diarrhea pneumonia otitis media meningitis neurological deafness

Can be complicated by various bone abnormalities; repeated serious infections, such as severe diarrhea, pneumonia, otitis media, meningitis, etc.; autoimmune diseases can occur, tumors can occur; may have mental retardation, neurological deafness, pyloric stenosis and liver disease.

Children with adenosine deaminase deficiency symptoms Common symptoms Limb shortening mental retardation meningitis diarrhea pyloric stenosis lung infection immunodeficiency infant rib valgus tremor deafness

According to the age of onset can be divided into 2 types:

1 early onset: onset within 1 week after birth;

2 late onset: late onset, clinical manifestations of ADA deficiency are the same as SCID, but the age, severity and consequences of the onset of the disease have a large degree of variation, 80% to 90% of children with typical SCID symptoms, some with With age growth (even to adulthood), the lack of enzymes gradually worsens clinical symptoms, and some ADA defects are "subclinical" patients.

ADA is completely deficient in the neonatal period, and is indistinguishable from other SCID clinical manifestations, but 50% have skeletal abnormalities, such as square skull, rib valgus, rib cartilage junction depression, incomplete closure, thoracolumbar spine, pelvic deformity And short-legged gnomes, etc., other manifestations of mental retardation, pyloric stenosis and liver disease, ADA activity retained 1% to 5% of patients with late-onset immunodeficiency, onset in infants 1 to 2 years old, immunoglobulin Sexual decline is its outstanding performance.

The clinical manifestations are mostly repeated and serious bacterial, fungal, viral and protozoal infections, severe diarrhea, pneumonia, otitis media, meningitis, etc.; animal experiments have confirmed that ADA defects can affect the lung metabolism of the sputum, causing alveolar macrophages Activation and infiltration of eosinophils can aggravate pulmonary infections and inflammatory reactions, eventually leading to alveolar dilatation and airway obstruction. Most children are susceptible to infection with Candida and cytomegalovirus, and some have Pneumocystis carinii infection. Some children may have symptoms of central nervous system, such as tremors, dance-like movements, and neurological deafness. Live vaccination may cause severe dissemination of infection.

Pediatric adenosine deaminase deficiency test

ADA lacks red blood cells in children, lymphocytes or fibroblasts have very low or no ADA activity. The erythrocyte ADA activity of carriers is about half of normal. Prenatal diagnosis can be made by measuring amniotic fluid fibroblasts or chorionic biopsy ADA enzyme activity. Genetic analysis can understand the location and type of genetic mutations and contribute to family surveys.

1. The lack of ADA in red blood cells is only 2% to 4% of normal red blood cells, and the ADA activity in other tissues is reduced to 10% to 30% of normal tissues. The measurement of ADA activity by amniocentesis is helpful for prenatal diagnosis.

2. Peripheral blood lymphocytes were significantly reduced in a small number of patients with eosinophils and poor platelet aggregation.

3. The blood Ig level is low, especially the lack of IgA and IgM, the specific antibody titer is reduced; the cellular immune function is significantly reduced, the PHA conversion of lymphocytes, and the delayed type hypersensitivity are negative.

X-ray examination can be found in the absence of thymus shadows, X-ray bone examination can find a variety of skeletal deformities; other X-ray examination according to clinical needs, can be found in lung lesions; EEG and brain CT examination can be found in the central nervous system Lesions, etc.

Diagnosis and differential diagnosis of adenosine deaminase in children

According to the corresponding clinical manifestations, cells, humoral immune function is low, white blood cells, red blood cells or cultured fibroblasts have low ADA activity, and the diagnosis can be confirmed.

Different from other types of SCID, it relies mainly on laboratory tests to confirm the diagnosis.

The material in this site is intended to be of general informational use and is not intended to constitute medical advice, probable diagnosis, or recommended treatments.