Pediatric arteriohepatic dysplasia syndrome

　　I. Etiology

　　This condition belongs to autosomal dominant inheritance.

　　II. Pathogenesis

　　1. The physiological function of bile excretion

　　Bile contains bile acid, which can increase bile secretion and promote the excretion of conjugated bilirubin, cholesterol, phospholipids, and other liposoluble organic substances (including some drugs) from bile. When bile acid enters the duodenum, it can emulsify fats and form water-soluble micelles with the products of fat digestion, so that fats can be absorbed by the intestinal mucosa. Bile acid is produced by the metabolism of cholesterol in the blood by liver cells, combines with glycine and taurine within the cells, and is excreted into the capillary bile duct, enters the intestine, assists in the absorption of fats, and most of it is absorbed at the end of the ileum, enters the portal vein and the intestinal-liver circulation, and can be reused. The reaction of liver cells converting cholesterol to bile acid is regulated by the concentration of blood bile acid; when the bile acid concentration increases, it can inhibit this reaction, and when it decreases, it promotes this reaction.

　　2, Pathophysiological and clinical characteristics

　　Biliary stasis can cause the following pathophysiological changes and clinical consequences.

　　(1) Substances normally excreted through bile are retained or refluxed into the body, causing an increase in blood concentration and the appearance of corresponding clinical manifestations. For example, hyperbilirubinemia can cause jaundice; hypercholerestolemia can cause pruritus; severe hypercholesterolemia can cause xanthomas. Serum phospholipids and lipoprotein X are increased. Excretion of certain drugs and contrast agents, such as sodium bromosulfophthalein (BSP), 131I rose bengal, etc., is also impaired.

　　(2) Decreased or absent bile in the intestine, and reduced conjugated bilirubin, can cause pale or grayish feces; reduced bile acids lead to malabsorption of fats and fat-soluble vitamins, causing steatorrhea, malnutrition, stunted growth and development, and deficiency of fat-soluble vitamins. Vitamin A deficiency can cause Bitot spots, keratinization of the skin and mucosa; D deficiency can lead to rickets and tetany; E deficiency can cause neuro muscular degeneration, proximal muscle atrophy; K deficiency can cause intracranial, gastrointestinal bleeding, and prolongation of blood clotting time.

　　(3) Liver cell injury caused by the primary disease and/or bile stasis in the bile ducts often leads to focal necrosis of the liver, hypertrophy of liver cells, splenomegaly, and abnormal liver function, such as elevated ALT, AST, alkaline phosphatase, 5'-nucleotidase, and alpha-fetoprotein, as well as impaired synthesis of albumin and coagulation factors. As the lesion progresses, it can develop into biliary cirrhosis, ultimately leading to portal hypertension and/or liver failure. However, most children can recover smoothly in clinical practice.

　　Patients with infantile arterial liver development abnormality syndrome can lead to delayed growth and development, intellectual development delay; the appearance of xanthomas; hypogonadism; often accompanied by congenital cardiovascular abnormalities, and must be treated in a timely manner.

　　The disease presents with persistent jaundice from birth, with pruritus generalis and skin lesions such as xanthomas, around 3 months old, indicating chronic intrahepatic bile stasis; characteristic appearance (prognathism, enophthalmos, increased interorbital distance, saddle nose, small chin, and projection forward); spinal deformity; delayed growth and development; intellectual development delay; hypogonadism; cardiovascular malformations: more than 80% are accompanied by congenital cardiovascular abnormalities, the most common being peripheral pulmonary artery stenosis, followed by patent ductus arteriosus, atrial or ventricular septal defects, tetralogy of Fallot, persistent truncus arteriosus, coarctation of the aorta, renal artery, coronary artery, and left subclavian artery stenosis, etc.

　　This condition is an autosomal dominant inheritance, and preventive measures should span from pre-pregnancy to prenatal and pre-marital physical examinations, which play a positive role in preventing birth defects. The extent of the role depends on the examination items and content, mainly including serological tests (such as hepatitis B virus, syphilis spirochete, HIV), reproductive system examinations (such as cervical inflammation screening), general physical examinations (such as blood pressure, electrocardiogram), and inquiries about family medical history and personal medical history, etc. Good genetic counseling work should be done.

　　1. Blood count

　　In the late stage of liver cirrhosis, the blood cell count may show a decrease in neutrophils and platelets.

　　2. Blood biochemistry test

　　There may be varying degrees of hyperbilirubinemia (34.2～256.5μmol/L), significantly elevated serum alkaline phosphatase, γ-glutamyl transpeptidase, and cholesterol. Transaminases may increase, and other liver proteins are usually normal. There may be mild hemolysis, prolonged coagulation time, and mild acidosis.

　　3. Other blood tests

　　Negative for hepatitis B virus infection, and negative for various etiological examinations.

　　4. X-ray examination and angiography

　　Cardiovascular malformations and spinal deformities were found in all cases, and other examinations should include abdominal ultrasound, electrocardiogram, and echocardiogram, which can clearly determine the type and extent of cardiovascular malformations.

　　Infants should be breastfed as the main food, with no excessive requirements. During the toddler period, attention should be paid to light and easily digestible foods, and an increase in protein and carbohydrate intake should be noted to meet the child's growth and development needs. It is also important to reduce the intake of lipid substances to avoid indigestion.

　　1. Treatment

　　Colestyramine (cholestyramine) combined with a low-fat diet can reduce jaundice and help absorb xanthoma and promote the growth and development of the child. There is no need for special treatment for peripheral pulmonary artery stenosis, and other cardiovascular malformations may require surgical treatment according to the condition.

　　2. Prognosis

　　The prognosis of this condition is good, jaundice can disappear in a few months or years later, but some may disappear only in adulthood, and generally does not lead to liver cell function failure.