Alagille syndrome

Alagille syndrome (ALGS) is a genetic disorder that affects primarily the liver and the heart. Problems associated with the disorder generally become evident in infancy or early childhood. The disorder is inherited in an autosomal dominant pattern, and the estimated prevalence of Alagille syndrome is 1 in every 30,000 to 1 in every 40,000 live births. It is named after the French pediatrician Daniel Alagille, who first described the condition in 1969. The severity of the disorder can vary within the same family, with symptoms ranging from so mild as to go unnoticed, to severe heart and/or liver disease that requires transplantation. It is uncommon, but Alagille syndrome can be a life-threatening disease with a mortality rate of 10%. The majority of deaths from ALGS are typically due to heart complications or chronic liver failure. Signs and symptoms arising from liver damage in Alagille syndrome may include a yellowish tinge in the skin and the whites of the eyes (jaundice), itching (pruritus), pale stools (acholia), an enlarged liver (hepatomegaly), an enlarged spleen (splenomegaly) and deposits of cholesterol in the skin (xanthomas). A liver biopsy may indicate too few bile ducts (bile duct paucity) or, in some cases, the complete absence of bile ducts (biliary atresia). Bile duct paucity results in the reduced absorption of fat and fat-soluble vitamins (A, D, E and K), which may lead to rickets or a failure to thrive. Cirrhosis and eventual liver failure is fairly common among ALGS patients, and 15% of those with severe hepatic manifestations require a liver transplant. Hepatocellular cancer has been reported in a small number of cases, but it is extremely rare. Common signs of Alagille syndrome include congenital heart problems varying from heart murmurs to significant structural abnormalities, such as Tetralogy of Fallot, Pulmonary Stenosis, overriding aorta, ventricular septal defect, and right ventricular hypertrophy are common amongst Alagille patients.