Pediatric alpha1-antitrypsin deficiency

Introduction to pediatric 1-antitrypsin deficiency 1-antitrypsindeficiency (1-antitrypsindeficiency) is an autosomal recessive hereditary disease characterized by cholestatic jaundice in infancy, progressive liver dysfunction and emphysema after adolescence. There is often a family history. basic knowledge The proportion of illness: 0.002% Susceptible people: infants and young children Mode of infection: non-infectious Complications: biliary cirrhosis, hemolytic anemia, emphysema

Pediatric 1-antitrypsin deficiency etiology

Causes:

The disease is an autosomal recessive hereditary disease. 1-AT is a polypeptide glycoprotein with a molecular weight of 52,000. It is synthesized in hepatocytes, secreted and released into serum, and maintains normal serum levels. Its normal serum concentration is 1.5. ~2.5g / L, the newborn is high 2.7g / L, it is the main component of serum 1-globulin, accounting for about 80% of 1 globulin, this enzyme belongs to the protease inhibitor system (protease inhibitor system) ), it inhibits trypsin, plasmin, thrombin, chymotrypsin, neutrophillastase, and the release of bacteria. Protein lysing enzymes, etc.

In the case of inflammation, tissue necrosis or injury, the serum concentration can be compensated by 2 to 4 times to eliminate excessive proteolytic enzymes released by various cells and bacteria to protect normal cells from such protein lytic enzymes. The damage is currently understood to have at least 33 alleles in the Pi system, M is the most common genotype, the most common in the normal population, PiMM type, about 95% in the United States is PiMM phenotype, its serum 1-AT The content is basically normal, the homozygous PiZZ type is the least, and the serum 1-AT is seriously deficient, less than 2mg/ml (only 10% to 20% of the normal value), and the serum 1-AT is obviously lacking due to the C-terminal of the molecule. After the lysine at position 53 is replaced by glutamate, the 1-AT homozygote can affect obstructive jaundice in infancy, and the serum of intermediate phenotype PiMZ, PiSZ, PiMS, etc. can only be as low as 1-AT. Normally less than 40%, usually without liver disease.

Pediatric 1-antitrypsin deficiency prevention

Tepson (1981) used intrauterine fetal blood to detect 1-AT and genotyping, and successfully made prenatal diagnosis, but intrauterine blood collection was dangerous and could not be universally applied; Kidd (1983) used amniotic fluid for cell culture and nucleic acid. Hybrid probe method, direct analysis of DNA, can make prenatal diagnosis, has been used in clinical, such as parental heterozygous PiMZ genotype, the first fetal PiZ suffering from severe liver disease that is difficult to cure, then the second child can still be 78% With liver disease, attention should be paid to genetic counseling and prenatal diagnosis.

Pediatric 1-antitrypsin deficiency complications Complications biliary cirrhosis hemolytic anemia emphysema

Homozygous complication is often complicated by cholestasis cirrhosis, complicated by hemolytic anemia, emphysema, polyarteritis and coagulopathy, and chronic active hepatitis.

Pediatric 1-antitrypsin deficiency symptoms Common symptoms Jaundice hardening liver splenomegaly Loss of appetite Liver function failure Nausea irritability Drowsiness sepsis barrel chest

Mainly for liver damage

Children often have non-surgical cholestasis-type hepatitis at 1 week of birth. The child has loss of appetite, sometimes nausea and vomiting, lethargy, irritability, jaundice and hepatosplenomegaly, dark urine, and white clay in the stool. Astragalus can gradually disappear after 2 to 4 months. The birth weight of these children is lower than normal, but it is not premature. The clinical findings are very similar to acute viral hepatitis or biliary atresia. The following situations can occur:

(1) Progression of the disease: A small number of children continue to progress, and symptoms of cirrhosis gradually appear within a few years, and die before the age of 6 due to liver failure or concurrent sepsis.

(2) Slow progression: Most patients have clinical remission and progression alternating with each other, and develop into chronic active hepatitis or cirrhosis after puberty.

(3) Heterozygous performance: Some patients, mostly heterozygous PiMZ or PiMS type, have different degrees of fibrosis in the liver stage in adulthood, but no obvious symptoms of cirrhosis.

2. Pulmonary syndrome

It is rare in children with emphysema, but there may be chronic pulmonary syndrome, but most of them occur in adults aged 30 to 40 years. The incidence of chronic obstructive emphysema in PiZZ homozygotes can reach 70% to 80%. Difficulty breathing, cough, diffuse emphysema and barrel chest, percussion is over-voiced; severe cases of clubbing (toe), growth and development disorders, etc.

3. Other

Some studies have indicated that the frequency of the PiZ allele is increased in adults with rheumatoid arteritis and juvenile chronic polyarteritis. Many coagulation abnormalities are associated with alpha1-AT deficiency, including platelet insufficiency, disseminated intravascular Coagulation and infant coagulopathy disorders, can show joint symptoms and bleeding tendency, family history of early liver and lung disease; serum 1-AT.

Pediatric 1-antitrypsin deficiency test

1. 1-AT: The serum 1-AT is reduced to less than 1.0 g/L, mostly PiZZ type, and the PiMZ type 1-AT is mostly between 1.0 and 2.0 g/L.

2. Blood examination: It shows the phenomenon of hypersplenism, and there are "three less" phenomena of red blood cells, white blood cells and thrombocytopenia.

3. Blood BSP: BSP excretion during cirrhosis is reduced.

4. Liver biopsy: PAS staining is positive, and eosinophilic small particles resistant to amylase in liver cells can be seen.

5. X-ray examination: visible emphysema and diaphragmatic drop, esophageal sputum can be seen esophageal varices.

6. Pulmonary function tests: varying degrees of damage.

Diagnosis and differential diagnosis of 1-antitrypsin deficiency in children

Giant cell inclusion disease and hepatitis, biliary atresia, choledochal cyst and various congenital metabolic diseases such as galactosemia, fructose intolerance, hepatic glycogen accumulation and hepatolenticular degeneration, etc. should be excluded. Respiratory symptoms should also be differentiated from immunodeficiency disease, pancreatic cystic fibrosis, esophageal malformation and esophageal hiatus hernia.

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