Alpha-1-antitrypsin deficiency

　　During protein electrophoresis, α1-AT is located within the α1-globulin band. α1-AT is a liver-synthesized glycoprotein with a half-life of about 4-5 days. There are substances in the serum that inhibit trypsin activity, of which α1-AT accounts for 90%. In addition to inhibiting trypsin activity, α1-AT can also inhibit chymotrypsin, factor XII auxiliary factor, and neutrophil elastase. α1-AT exists in tears, duodenal juice, saliva, nasal secretions, cerebrospinal fluid, lung secretions, and breast milk. The concentration of α1-AT in amniotic fluid is equivalent to 10% of serum. Inflammation, tumor, pregnancy, or estrogen therapy can increase the concentration of α1-AT in serum by 2-3 times, but these stimuli are almost ineffective for patients with α1-AT deficiency.

　　In the normal human body, there are exogenous and endogenous proteases, such as bacterial toxins and proteases released from leukocyte lysis, which have destructive effects on the liver and other organs. α1-AT can antagonize these enzymes to maintain the integrity of tissue cells. When α1-AT is deficient, these enzymes can erode liver cells, especially in newborns whose intestinal cavity digestion and absorption function is not完善, more macromolecular substances enter the blood, and the liver of infants with α1-AT deficiency is more susceptible to damage. In addition, α1-AT also has the function of regulating immune responses, affecting the clearance of antigen-antibody immune complexes, complement activation, and inflammation. It can also inhibit platelet aggregation and the occurrence of fibrinolysis. When α1-AT is deficient, the mechanism of body balance mentioned above is dysregulated, leading to tissue damage.

　　The pathological feature of the liver is that there are round or oval deposits in the liver cells around the lobules, with a diameter of 1-40μm. These spherical particles increase in size with age and are more easily seen as the infant matures. HE staining shows eosinophilic staining in the cytoplasm of liver cells, and PAS staining is most clearly resolved after treatment with amylase.

　　Immunofluorescence and immunocytochemistry show that the inclusions are α1-AT, and these inclusions can also be seen in heterozygotes. The density and extent of these inclusions seem to have no definite relationship with the presence or absence of liver disease, but the absence of these inclusions indicates no occurrence of liver disease, suggesting that these inclusions may play a certain role in the pathogenesis of the disease.

　　Under the electron microscope, it can be seen that the rough endoplasmic reticulum within the liver cells is expanded and contains characteristic deposits of varying morphologies, while no such deposits are found in the Golgi apparatus. The amount of deposits varies greatly among individuals, and they can also be seen in bile duct cells. In addition, glycogen, vacuoles, lipofuscin, and bile stasis can also be seen in the liver cells.

　　Newborns with Pizz phenotype, if accompanied by cholestatic jaundice due to α1-AT deficiency, the liver shows the following three pathological manifestations:

　　One: Liver cell injury

　　The characteristics are the enlargement of liver cells, relatively mild inflammatory cell infiltration, and mostly mononuclear cell infiltration. It can be accompanied by or without liver fibrosis, and there may be cholestasis, but no bile thrombus formation in the portal area.

　　Two: Portal fibrosis of the liver and bile duct hyperplasia

　　There is extensive portal area fibrosis, even with manifestations similar to liver cirrhosis, with obvious bile duct hyperplasia. Jaundice regressed 6 months ago, but the liver and spleen have progressively enlarged and hardened. There have been two cases of portal hypertension, but there is no abnormality in the extrahepatic bile ducts in such patients.

　　3. Maldevelopment of small bile ducts

　　The liver structure is normal, with slight liver cell damage, only slight fibrosis at the portal area, but the number of bile ducts is significantly reduced, bile stasis is scattered within the liver lobules, and the clinical course is progressive jaundice, accompanied by itching and hypercholesterolemia.

　　Patients are prone to complications such as hepatitis, cholestasis jaundice, liver cirrhosis, liver cancer, emphysema, upper gastrointestinal bleeding, or hepatic coma.

　　The main damage is to the liver: the child can often have non-surgical cholestasis hepatitis within one week of birth. The child has poor appetite, and sometimes nausea and vomiting, drowsiness, irritability. Jaundice and enlargement of the liver and spleen occur. The urine is deep yellow, and the stool is clay-colored. Jaundice can persist for 2 to 4 months and gradually fade. Most of these children are born with a weight lower than normal, but not premature.

　　Pulmonary syndrome is rare in children with emphysema, but chronic pulmonary syndrome can occur, but it mostly occurs in adults aged 30 to 40.

　　The frequency of the PiZ allele in patients with rheumatic fever-like arteritis and juvenile chronic polyarteritis increases. Many coagulation abnormalities are associated with α1-AT deficiency, including platelet dysfunction, disseminated intravascular coagulation, and infantile coagulation system disorders.

　　α1-antitrypsin deficiency can cause cholestasis jaundice in the first week after birth, with non-colored stools, deep urine color, and physical examination may reveal liver enlargement. Biochemical indicators show signs of obstructive jaundice. Jaundice often disappears from 2 to 4 months, and liver cirrhosis can appear after 2 years.

　　In adults, most patients with α1-AT deficiency present with prominent portal hypertension as the initial manifestation, and they often die of upper gastrointestinal bleeding and/or hepatic coma. Pneumonectomy often occurs, and the incidence of liver cirrhosis and liver cancer in males is higher than in females.

　　Patients with liver cirrhosis caused by α1-AT deficiency have a high incidence of liver tumors, most of which originate from liver cells, with some originating from bile ducts.

　　Preventive measures for α1-antitrypsin deficiency include smoking cessation, removal of factors that can cause respiratory tract obstruction, prevention of bronchopulmonary infections, and evaluation of overall health. α1-antitrypsin deficiency is an autosomal dominant hereditary disease, and the following preventive measures should be taken:

　　1. Pre-marital health examination

　　Couples who have established a romantic relationship should undergo a comprehensive and systematic health examination before applying for marriage registration procedures. It is particularly important to avoid marriage between close relatives. The offspring of close relatives are more likely to have intellectual disability, congenital malformations, and various hereditary diseases than those of non-close relatives, several times more.

　　2. Pre-pregnancy genetic counseling

　　Both parties or one party, if there is a hereditary disease patient among their relatives, are worried about whether they will give birth to a child with the same hereditary disease after marriage, and should consult whether they can marry and if the consequences of marriage will be very serious; one party of the two has a certain disease, but does not know whether it is a hereditary disease, whether they can marry, and what is the chance of passing it on to offspring. The doctor will make an explicit diagnosis and inform of reasonable treatment methods.

　　3, Prenatal screening can prevent the birth of children with defects

　　Prenatal screening is mainly aimed at some diseases that currently have no good treatment methods, and its purpose is to prevent the birth of defective children. It is generally carried out between 16 and 20 weeks of pregnancy, with 2-3 milliliters of peripheral blood from the pregnant woman being taken for examination. If a high-risk possibility (high-risk factors exceeding 1/270) is found, further amniocentesis is needed for confirmation.

　　Alpha-1-antitrypsin deficiency can be diagnosed by normal alpha-1-AT content determination and Pi phenotype analysis. Liver biopsy shows liver cells filled with spherical red bodies of different sizes, with positive PAS staining. The following is the specific content:

　　1, The serum alpha-1-AT is reduced to less than 1.0g/L in most PiZZ types, while PiMZ types of alpha-1-AT are usually between 1.0 and 2.0g/L.

　　2, Blood count shows hyperactivity of the spleen, with the phenomenon of 'three less' (decreased red blood cells, white blood cells, and platelets).

　　3, Blood BSP excretion is reduced in the liver cirrhosis stage.

　　4, Liver biopsy shows PAS-positive staining, with eosinophilic granules resistant to amylase in liver cells.

　　5, X-ray examination shows emphysema in both lungs and descent of the diaphragm. Barium esophagram shows esophageal varices.

　　6, There is varying degrees of damage to lung function.

　　Food suitable for patients with liver disease:

　　Apples are rich in potassium, which can excrete excess sodium in the body and maintain normal blood pressure.

　　Oats contain a high amount of linoleic acid and a rich amount of saponins, which can reduce serum cholesterol and triglycerides.

　　Corn is rich in calcium, selenium, lecithin, vitamin E, and other nutrients, which have the effect of reducing serum cholesterol.

　　Kelp contains a lot of taurine, which can reduce cholesterol in blood and bile; the dietary fiber alginate can inhibit the absorption of cholesterol and promote its excretion.

　　Garlic contains a mixture of sulfur compounds that can reduce blood cholesterol, prevent thrombus formation, and help increase the content of high-density lipoproteins. Apples are rich in potassium, which can excrete excess potassium salts in the body and maintain normal blood pressure.

　　Milk contains a lot of calcium, which can inhibit the activity of cholesterol synthesis enzymes in the human body, thereby reducing the absorption of cholesterol in the human body.

　　The allyl disulfide and sulfur-containing amino acids in onions not only have bactericidal properties but can also lower blood lipids and prevent atherosclerosis; they can activate the active components of fibrinogen, effectively preventing the formation of thrombi in blood vessels; prostaglandin A also has a good blood pressure-lowering effect on the human body.

　　Sweet potatoes can neutralize the excess acid produced in the body due to excessive consumption of meat and eggs, maintaining the acid-base balance in the human body. Sweet potatoes contain a lot of fiber, which can absorb a lot of water in the gastrointestinal tract, lubricate the digestive tract, have a laxative effect, and can also excrete excessive fat, sugar, and toxins from the body, thereby reducing blood lipids.

　　Foods that liver patients should not eat:

　　For liver patients, nutrient-rich foods can help repair liver cells, but some foods should not be eaten in large quantities. It is necessary to control the amount, and eating too much can反而 affect the recovery of liver disease.

　　1. Chocolate, sugar, and various sweets should not be eaten in large quantities within a day. Eating too much can disrupt the secretion of digestive enzymes in the gastrointestinal tract, affecting appetite; sugar is easy to ferment, can加重 gastrointestinal bloating, and is prone to be converted into fat, accelerating the storage of fat by the liver, and promoting the occurrence of fatty liver.

　　2. Eat less sunflower seeds. Sunflower seeds contain unsaturated fatty acids, and eating too much can consume a large amount of choline in the body, making it easier for fat to accumulate in the liver and affecting the function of liver cells.

　　3. Preserved eggs contain a certain amount of lead, which can replace calcium in the human body. Regular consumption of preserved eggs can lead to calcium deficiency and osteoporosis, and can also cause lead poisoning.

　　4. Monosodium glutamate is a good seasoning, but if liver patients take it in large quantities or in excessive amounts, it can cause transient headaches, palpitations, and even nausea.

　　5. Instant noodles, sausages, and canned foods often contain food dyes and preservatives that are harmful to the human body. Regular consumption will increase the burden on the liver's metabolism and detoxification function.

　　6. Various preserved foods have too much salt, and eating too much can affect water and sodium metabolism, and should be禁忌 for decompensated liver cirrhosis patients.

　　7. It is not advisable to eat wheat, potatoes, and other foods.

　　Currently, there is no effective therapy, so the best way is to avoid the occurrence of α1-AT deficiency. If the parents are Pizz heterozygotes, there is a 225% chance that their children will have the Pizz phenotype. At the gestational age of 15 to 17 weeks, the umbilical cord blood of the fetus can be directly taken for Pizz phenotype analysis, which has a definite value for terminating pregnancy of fetuses with a risk of onset. For α1-AT deficiency patients, a promising treatment method is:

　　1. Liver transplantation;

　　2. Use the method of genetic engineering to implant the Z gene into patients to produce α1-AT;

　　3. Genetic recombination.