Wilson disease is characterized by abnormal storage of copper in the liver, leading to hepatocellular injury, CNS dysfunction, and hemolytic anemia. It is an autosomal recessive trait caused by mutations in the ATP7B gene. The encoded protein of this gene functions as an ATP-driven copper pump. The diagnosis is made by identifying depressed serum levels of ceruloplasmin, elevated 24-hour urine copper excretion, the presence of Kayser-Fleischer rings in the iris, evidence of hemolysis, and elevated hepatic copper content. In any single patient, one or more of these measures may be normal. Clinical presentation also varies, but seldom occurs before age 3 years. Neurologic abnormalities may predominate, including tremor, decline in school performance, worsening handwriting, and psychiatric disturbances. Anemia may be the first noted symptom. Hepatic presentations include appearance of jaundice, spider hemangiomas, portal hypertension and its consequences, and fulminant hepatic failure. Treatment consists of administration of copper-chelating drugs (penicillimine or trientine), with monitoring of urine copper excretion at intervals. Zinc salts often replace chelating agents after chelation therapy has successfully reduced excessive body copper stores. Adequate therapy must be continued for life to prevent liver and CNS deterioration.
Immune-mediated liver injury may be primary or occurin association with other autoimmune disorders, such as inflammatory bowel disease or systemic lupus erythematosus.Diagnosis is made on the basis of elevated serum total IgGand the presence of an autoantibody, most commonly antinuclear, anti–smooth muscle, or anti–liver-kidney microsomal antibody. Liver biopsy specimen shows the presence ofa plasma cell–rich portal infiltrate with piecemeal necrosis.Treatment consists of corticosteroids initially, usually withthe addition of an immunosuppressive drug after remissionis achieved. Steroids are tapered gradually as tolerated tominimize glucocorticoid side effects. Many patients require lifelong immunosuppressive therapy, but some may be able tostop medications after several years under careful monitoringfor recurrence.
Steatohepatitis, also known as nonalcoholic fatty liver disease or nonalcoholic fatty hepatitis, is characterized by the presence of macrovesicular fatty change in hepatocytes on biopsy. Varying degrees of inflammation and portal fibrosis may be present. This disorder occurs in obese children, sometimes in association with insulin-resistant (type 2) diabetes and hyperlipidemia. Children with marked obesity, with or without type 2 diabetes, who have elevated liver enzymes and no other identifiable liver disease are likely to have this condition. Nonalcoholic fatty liver disease can progress to significant fibrosis. Treatment is with diet and exercise. Vitamin E may have some benefit. Efforts should be made to control blood glucose and hyperlipidemia and promote weight loss. In general, the rate of progression to end-stage liver disease is slow.
The cause of inadequate pancreatic digestive function in 95%of cases is cystic fibrosis (see Chapter 137). The defect in CFTR chloride channel function results in thick secretions in the lungs, intestines, pancreas, and bile ducts. In the pancreas, there is destruction of pancreatic function, oftenbefore birth. Some mutations result in less severe defects in CFTR function and later onset of lung disease and pancreatic insufficiency. Less common causes of pancreatic insufficiency are Shwachman-Diamond syndrome and Pearsonsyndrome in developed countries and severe malnutrition indeveloping countries.
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Failure to Thrive