Congenital nonhemolytic jaundice

Introduction to congenital non-hemolytic jaundice Congenital non-hemolytic jaundice (Gilbert syndrome), a group of comprehensive diseases, was first reported by French physician Gilbert in 1092 as jaundice caused by non-hemolytic and non-binding bilirubinemia. 25% to 50% of congenital patients have this disease and are autosomal dominant genetic diseases. From a strict definition, it is characterized by non-hemolytic, non-binding hyperbilirubinemia, while serum cholic acid is normal and liver function is normal. basic knowledge The proportion of illness: 0.0003% (the incidence rate of newborns is 0.0003%) Susceptible people: children Mode of infection: non-infectious Complications: hemolytic anemia

Congenital non-hemolytic jaundice

(1) Causes of the disease

Genetic factors (45%)

The phenomenon that the biological parents are similar to the offspring and between the offspring, and the progeny's traits can be expressed in the next generation. Genetic material was passed from generation to generation. At present, most people believe that congenital non-hemolytic jaundice is related to heredity.

Hepatocyte uptake and binding function defects (45%)

Insufficient activity of bilirubin glucuronyltransferase in microsomes in acquired hepatocytes affects the normal binding of unbound bilirubin in hepatocytes, so that the uptake of bilirubin by hepatocytes is also impeded. Thus, it causes double defects in the uptake and binding function of hepatocytes to unbound bilirubin.

(two) pathogenesis

In all patients with liver biopsy specimens, it was confirmed that the activity of bilirubin glucuronyltransferase in the liver was significantly reduced, suggesting that the liver's ability to clear indirect bilirubin from plasma is reduced, but the concentration of plasma unconjugated bilirubin is decreased. There is no significant relationship with the degree of activity reduction of this enzyme, which may be due to the presence of moderate compensatory hemolysis in some patients with Gilbert syndrome; bilirubin transport kinetics suggest that non-binding hyperbilirubinemia The cause of the disease is not due to excessive production, but due to transport defects, and on the other hand, some patients have abnormal BSP transport, which also indicates that some patients in this syndrome have transport function defects, because free bilirubin enters liver cells. It is carried by the two low-molecular soluble "receptor proteins" (accepted by Y, Z protein) in the hepatocyte cytoplasm to the smooth endoplasmic reticulum, and combined under the action of enzymes. If the amount of Y, Z protein is insufficient or the function is poor. At the time, the transportation disorder will also affect the uptake and binding of unconjugated bilirubin by hepatocytes. According to the concentration of serum bilirubin, the syndrome can be divided into two types. Its pathogenesis may be different.

1. Lighter and more severe, serum bilirubin is lower than 85.5mol/L, and the urinary biliary tract is normal. The pathogenesis may be defective in the process of hepatocyte uptake and transport of unconjugated bilirubin, such as hepatocyte cytoplasm. Insufficient soluble protein receptor or its dysfunction, causing transport disorder of unbound bilirubin in hepatocytes, affecting the uptake of unconjugated bilirubin by hepatocytes, but there may be some mild patients The pathogenesis of the critically ill patients is the same, which is due to the insignificance of glucuronyltransferase activity, but it is related to the decrease of extremely mild enzyme activity due to the lack of sensitive detection technology.

2. Heavy serum bilirubin is greater than 85.5mol/L (5mg/dl), often appearing in the neonatal period, due to the lack of glucuronidase activity in the microsomes in hepatocytes, resulting in hepatocyte binding function Poor, causing jaundice with unconjugated bilirubin hyperemia.

Congenital non-hemolytic jaundice prevention

1. It is also crucial to conduct the pre-marital medical examination and prenatal diagnosis in a timely manner. Such as ultrasound monitoring, chromosome examination, etc.

2, should not drink alcohol, smoking, fatigue, medication, etc. before pregnancy, should avoid colds, direct sunlight, high temperature, away from chemical and harmful substances during pregnancy.

3. Give the child bilirubin, blood routine, ultrasound monitoring, etc. after delivery.

Congenital non-hemolytic jaundice complications Complications hemolytic anemia

There may be mild hemolytic anemia.

Congenital non-hemolytic jaundice symptoms common symptoms jaundice bile excretion obstruction obstructive jaundice easy fatigue dyspepsia hemolytic anemia

Mainly manifested as chronic intermittent jaundice from childhood, can be recessive; jaundice can persist for the elderly, but tends to gradually decline with age, serum bilirubin is lower than 102.6mol / L, generally less than 51.3 Molmol/L, with day or night or seasonal fluctuations, about 1/3 of cases are normal during routine examination, due to fatigue, mood swings, hunger, infection, fever, surgery, alcohol abuse, pregnancy induced or aggravated jaundice.

The general condition of the patient is acceptable, and there are no obvious symptoms. Some patients may be accompanied by fatigue, liver discomfort, indigestion, etc. Sometimes patients with Gilbert syndrome may also be accompanied by mild hemolytic anemia.

Except for occasional dominant jaundice, no abnormal signs, liver and spleen often do not enlarge.

According to the different concentrations of serum bilirubin, the syndrome can be divided into light and heavy, lighter and more severe, serum bilirubin is less than 85.5mol / L; heavy serum bilirubin is greater than 85.5mol / L, often Jaundice occurs during the neonatal period.

Examination of congenital non-hemolytic jaundice

In most cases, jaundice is mild, serum total bilirubin is 22.1-51.3mol/L, and a few to 85-102mol/L or higher, mainly due to elevated blood unconjugated bilirubin, normal serum bile acid, and other livers. Functional tests were normal (such as ALT, AST, and -GT), no evidence of hemolysis, normal erythrocyte fragility test, urinary bilirubin negative, normal urinary biliary volume in the feces, and no increase in urinary urinary tract.

1. Gallbladder development is good, gallbladder angiography can be no abnormalities.

2. Phenobarbital test: phenobarbital can induce liver microsomal glucuronyltransferase activity, promote unconjugated bilirubin and glucuronic acid, reduce plasma unconjugated bilirubin concentration, oral phenyl b 2 weeks, 3 times / d, each time 60mg; after taking the drug to determine the concentration of plasma bilirubin, most patients with jaundice improved, serum indirect bilirubin decreased significantly, even up to normal; such as the complete lack of UGT1 If caused by jaundice, it is invalid.

3. Low-calorie diet test: 1674kJ (400kcal) diet is given every day for 2~3 days. If the plasma indirect bilirubin value increases by more than 100%, or increases by 25.65mol/L, it has diagnostic significance. After returning to normal diet for 12~24h, Down to the basal level, the sensitivity of the low-calorie diet test to the disease is about 80%, the specificity is up to 100%, and the mechanism of serum bilirubin elevation in patients with Gilbert syndrome caused by starvation may be multifactorial, and the following causes caused by starvation Changes related: intrahepatic bilirubin ligand and Z protein content decreased; heme catabolism increased; adipose tissue lipolysis, increased free fatty acids, causing bilirubin to release and release into the circulation; intestinal peristalsis weakened, bilirubin Increased liver circulation.

4. The Gilbert syndrome patients were dosed with radionuclide-labeled indirect bilirubin and the percentage of plasma retention in 24 hours after Gilbert syndrome was higher than in normal subjects.

5. There was no obvious change in liver biopsy. Even a small amount of fatty changes were observed. Even in the terminal hepatic vessels, there was lipofuscin-like pigmentation. Liver biopsy was used to measure the activity of bilirubin glucuronyltransferase. The vitality was significantly lower than that of normal people. Electron microscopy showed that the rough endoplasmic reticulum and the protein particles on the liver cells were significantly reduced, and the smooth endoplasmic reticulum increased hypertrophy.

Diagnosis and diagnosis of congenital non-hemolytic jaundice

Diagnostic criteria

Because the disease can be confused with some diseases with clinical consequences, resulting in treatment errors, clinical diagnosis is more important. The following points are highly suggestive of Gilbert syndrome:

1. Chronic intermittent or fluctuating mild jaundice, with seizure incentives, may have a family history, general condition, no obvious symptoms.

2. Physical examination Except for mild jaundice, there are no other abnormal signs, and the liver and spleen are not much.

3. General liver function (ALT, AST, AKP, bile acid) is normal, and only the fluctuation of plasma unconjugated bilirubin level is increased.

4. No hemolysis, hepatocellular, obstructive jaundice evidence.

5. Liver histopathology was normal.

For example, after 2 to 3 visits in 12 to 18 months, no other laboratory abnormal findings can be diagnosed as Gilbert syndrome. Detection of TATAA sequence or gene mutation in UGT1 promoter is helpful for diagnosis.

Differential diagnosis

Need to be differentiated from chronic non-binding hyperbilirubinemia caused by fatty liver, alcoholism, chronic cholecystitis, cirrhosis and viral hepatitis; need to be differentiated from chronic hemolytic jaundice, the latter in addition to indirect bilirubin In addition, there is anemia, reticulocyte increased, urinary urinary biliary tract also increased, some serum pathogenic virus hepatitis was misdiagnosed as Gilbert syndrome because: the history is unknown, one-sided attention to treatment trials and starvation test Lack of attention to liver biopsy.

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