Pediatric purine nucleotide phosphorylase deficiency
Introduction
Introduction to sputum nucleotide phosphorylase deficiency In the absence of purine nucleoside phosphorylase (PNP), T cell immune function is defective and B cells may be normal. The disease was first reported in 1975 as an autosomal recessive disorder. basic knowledge Sickness ratio: 0.001%-0.002% Susceptible people: children Mode of infection: non-infectious Complications: ataxia, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia
Cause
Pediatric nucleotide phosphorylase deficiency cause
(1) Causes of the disease
PNP deficiency leads to accumulation of the nucleotide metabolite dGTP, which is toxic to early T cells and B cells, arresting its development in the pro-T/pro-B phase, leading to defects in T cells and B cells.
(two) pathogenesis
Because T cells are more sensitive to PNP than B cells, PNP deficiency is mainly caused by cellular immunodeficiency. Similar to ADA, PNP is involved in the purine metabolism pathway, ADA catalyzes the transamination of adenine to inosine, and inosine is converted to PNP. Astragalus, PNP is present in all cells, and there are many lymphocytes. PNP deficiency is relatively less harmful to B cells. The contradiction is mainly the accumulation of intracellular toxic metabolites and the selectivity of deoxyadenine and deoxyguanine to different tissues. Toxicity, the immune function of children with PNP deficiency changes with time. Many patients have normal T and B cells at an early age, and their immune function gradually deteriorates with age.
The gene encoding PNP is located at 14q13 and consists of 6 exons. The DNA is 9 kb long. The PNP-deficient gene mutation is a point mutation causing amino acid substitution. Each patient is a PNP allele mutation, only one site mutation. Not enough to cause disease, heterozygous parental PNP enzyme activity is normal 1/2, but no clinical manifestations.
Prevention
Pediatric sputum nucleotide phosphorylase deficiency prevention
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.
3. Prenatal diagnosis Some immunodeficiency diseases can be prenatally diagnosed, such as cultured amniotic fluid cell enzymology can diagnose adenosine deaminase deficiency, nucleoside phosphorylase deficiency and some combined immunodeficiency diseases; Blood cell immunological test can diagnose CGD, X-linked no-gammaglobulinemia, severe combined immunodeficiency disease, thereby stopping pregnancy, preventing the birth of children, the prognosis of this disease is very poor, should be accurately diagnosed early, and given specific treatment early It is very important to provide genetic counseling (prenatal diagnosis or even intrauterine treatment). The determination of PNP activity in amniotic fluid fibroblasts is helpful for prenatal diagnosis, and its molecular defects can be directly detected by PCR.
Complication
Pediatric sputum nucleotide phosphorylase deficiency complications Complications, ataxia, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia
Repeated serious infections, often complicated by nervous system damage, including convulsions, hemiparesis, developmental delay, ataxia, tremors and ADHD, can be combined with lupus arthritis and pericarditis, central nervous system vasculitis, autoimmune hemolytic anemia , idiopathic thrombocytopenic purpura, etc.; and growth disorders and malignant tumors.
Symptom
Pediatric sputum nucleotide phosphorylase deficiency symptoms Common symptoms Repeated infection of granulocytes to reduce thrombocytopenia tremor pericarditis ataxia
The most important clinical manifestation of PNP deficiency is repeated infection, which usually begins in the first year after birth. Some patients begin clinical manifestations several years after birth. The infection type is the same as SCID. The special pathogens include Pseudomonas, cytomegalovirus, Varicella, adenovirus, Epstein-Barr virus, ECHO virus, Candida and Pneumocystis carinii, most children can receive routine immunization, produce antibodies against tetanus and poliovirus, and do not necessarily occur after inoculation with BCG. Diffusion, neurological diseases are very common, including convulsions, hemiparesis, developmental delay, ataxia, tremors and ADHD, autoimmune diseases including lupus arthritis and pericarditis, central nervous system vasculitis, autoimmune hemolytic Anemia, idiopathic thrombocytopenic purpura, and neutropenia, growth disorders are another clinical problem of PNP deficiency, and physical examination can affect smaller lymph nodes.
Examine
Pediatric sputum nucleotide phosphorylase deficiency test
1. The diagnostic index of dGTP in lymphocytes is increased. The PNP enzyme activity of red blood cell lysate can be used to diagnose the disease. The lack of PNP in red blood cells is the indication for the diagnosis of this disease. The PNP activity of amniotic fluid and wool membrane cells can be used for prenatal diagnosis. However, the molecular defects can be directly detected by PCR. 2. Urine urinary acid excretion is reduced by urine, while guanosine, deoxyguanosine and inosine, deoxyinosine are discharged, and the above methods are detected by various methods such as high performance liquid chromatography. Metabolites contribute to the diagnosis of this disease.
3. Blood examination The number of white blood cells is normal, but the percentage of lymphocytes is extremely low (<10%). The function of T cells can be normal at birth. The number of T cells can often be as low as 1% to 3% with age. Also significantly decreased, the majority of patients B percentage, immunoglobulin levels and specific antibodies are normal, blood Ig levels, B cells and plasma cells are basically normal, peripheral blood T cells, Ts cells decreased, lymphocyte PHA conversion The allogeneic mixed lymphocyte reaction was reduced, and the delayed type hypersensitivity was negative.
4. Pathological examination showed thymic dysplasia, lack of thymus corpuscles, lymph node thymus-dependent areas dysplasia, lymphocytes are rare; non-thymus-dependent areas are rich in lymphocytes and plasma cells.
According to clinical manifestations, chest X-ray, B-ultrasound, brain CT, EEG, electrocardiogram, etc. were selected.
Diagnosis
Diagnosis and identification of sputum nucleotide phosphorylase deficiency in children
According to the history of repeated infections in infancy, clinical manifestations, lymphocyte dGTP, erythrocyte PNP determination and other laboratory tests can establish a diagnosis.
Different from other types of SCID, it relies mainly on laboratory tests to confirm the diagnosis.
