Alagille Syndrome

Alagille syndrome is a genetic disorder that affects the liver, heart, and other systems of the body. 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 70,000 live births.

Autosomal dominant

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 requiring transplantation.

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, and deposits of cholesterol in the skin (xanthomas). A liver biopsy may indicate too few bile ducts (bile duct paucity). Other signs of Alagille syndrome include congenital heart problems, particularly Tetralogy of Fallot, and an unusual butterfly shape of the bones of the spinal column that can be seen in an x-ray. Many people with Alagille syndrome have similar facial features, including a broad, prominent forehead, deep-set eyes, and a small pointed chin. The kidneys and central nervous system may also be affected.

Mutations in the JAG1 gene cause Alagille syndrome. The JAG1 gene is involved in signaling between adjacent cells during embryonic development. This signaling influences how the cells are used to build body structures in the developing embryo. Mutations in JAG1 disrupt the signaling pathway, causing errors in development, especially of the heart, bile ducts in the liver, spinal column, and certain facial features.

Narrowed and malformed bile ducts in the liver produce many of the health problems associated with Alagille syndrome. Bile is produced in the liver and moves through the bile ducts into the small intestine, where it helps to digest fat. In Alagille syndrome, the bile builds up in the liver and causes scarring that prevents the liver from working properly to eliminate wastes from the bloodstream.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.

See also

• Progressive familial intrahepatic cholestasis

External Links

• Alagille Syndrome, Liver Diseases and Treatments, Cincinnati Children's Hospital Medical Center

Support groups

• Allagille Syndrome Alliance

• LIVER FAMILIES: An online support group for families whose lives have been touched by pediatric liver disease and transplant.

This article incorporates public domain text from The U.S. National Library of Medicine

NIH genetic and rare disease info

• NIH info on Alagille Syndrome

Alagille Syndrome is a rare disease.