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Alagille Syndrome
Thursday, 05 August 2004
Thursday, 05 August 2004

What

Alagille syndrome (AGS) is a rare, genetically inherited disease. It is a disorder that affects many different organ systems, primarily the liver, heart, eyes, face, spinal skeleton and kidneys. The main problem people with AGS have is that they have fewer bile ducts in the liver than normal. The other features of AGS are highly variable from person to person.

Who

The incidence of AGS is one in about every 75,000 births. The disease affects both boys and girls equally. It is one of the most common inherited disorders that cause reduced bile flow within the liver. AGS has been identified as a genetic disorder that is inherited from one parent. Every one has two copies of one gene. A disorder in one copy of the AGS gene will give a person the disease whether or not they have a normal other copy of the AGS gene. Thus the mode of inheritance is known as autosomal dominant. This means that usually one of the child’s parents has the disorder, and their child inherits it. Parents may have few symptoms of the disease though because of the variability from person to person.

Signs and Symptoms

Babies are usually diagnosed soon after birth because of the presence of jaundice (yellow skin color). Common signs and symptoms within the first three months may range in severity and include: 1. Jaundice, usually present at birth 2. Severe itching 3. Pale, loose or clay-colored stools 4. Poor weight gain 5. Poor growth 6. Deficiency of vitamins A, D, E and K which may result in vision problems, rickets, and poor clotting of blood 7. Heart problems (usually pulmonary stenosis, a narrowing of the arteries that lead from the heart to the lungs) In some children, certain symptoms may not become apparent until early childhood or adolescence. These symptoms include: 1. Jaundice persists 2. Growth and development problems 3. Enlarged liver 4. Hard, whitish nodules (xanthomas) that develop in the skin in spots of frequent trauma like knees and elbows 5. Dark yellow or brown urine 6. Persistent itching

Possible Causes

AGS results in a lack of normal bile ducts within the liver. Bile helps absorb fats and vitamins from our diet. The bile is produced by the liver and then travels through small tubes in the liver to one large tube that empties into the small intestine and helps with absorption of fats and vitamins. In people with AGS, the lack of small bile ducts inside the liver slows down the flow of bile from the liver to the intestines. This malfunction results in a build up of bile in the liver and the rest of the body. This damages the liver, and could eventually lead to liver failure.

Diagnosis

A diagnosis of AGS is made based on either tests or a physical examination. While reduced bile flow is the main symptom of AGS, two things are necessary for a diagnosis of AGS. First, a liver biopsy showing a reduction in bile ducts in the liver is necessary to make a definitive diagnosis. Alagille syndrome patients also have at least three of the following five characteristics: 1. Reduced bile flow 2. Cardiac defect (pulmonary stenosis) 3. Skeletal abnormalities (most commonly butterfly vertebrae) 4. Vision abnormalities 5. Characteristic facial features Liver function tests also can be used to assess the state of the liver and bile function. A nuclear scan may be done to show how much bile is flowing from the liver. A highly specialized test called a bile salt screen may be done to pinpoint AGS from other conditions that cause liver disorders. Genetic testing is not routinely used although the gene for AGS has been identified. It is critical to note that AGS is a very variable disease even within a family.

Treatment

: The treatment of AGS involves management of the symptoms and preventing any further complications. This strategy includes using medicine to increase bile flow and relieve the severe itching due to build up of bile in the blood and skin and nodules that develop under the skin. Vitamin supplements are used because reduced bile leads to difficulties in absorption of vitamins A, D, E, and K. People with AGS are often on specific diets that include very high caloric intake and baby formulas that are rich in triglycerides. Approximately one third of people with Alagille syndrome will eventually require a liver transplant. Although there is no cure for AGS, research is ongoing to try to use gene therapy to find a cure.

Prognosis

: The prognosis of AGS is variable and depends on the severity of the bile duct malfunction and damage to the liver. Furthermore, the presence and severity of other problems like cardiac and lung problems can significantly affect the prognosis. Typically a person with AGS has worsening bile flow at first but often there is improvement later in the course of the disease. Children with AGS generally have a better outcome than children with other liver disorders at the same age. Many adults with AGS lead normal lives with appropriate dietary management.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

The Official Alagille Syndrome Alliance Worldwide Web Site.
Great website for parents with links to medical info and research and support group information.

Children's Liver Association for Support Services
C.L.A.S.S. is an all-volunteer, nonprofit organization dedicated to serving the emotional, educational, and financial needs of families coping with childhood liver disease and transplantation.

American Liver Foundation
A great site with detailed information about the disease, treatment options and support groups.

Google Search for Alagille Syndrome

References and Sources

www.geneclinics.org/profiles/alagille/ www.emedicine.com/ped/topic60.htm www.cincinnatichildrens.org/svc/prog/liver/diseases/alagille-syndrome.htm www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=118450