Alagille syndrome is a disease in which the liver has too few bile ducts. Children with Alagille syndrome will typically experience a progressive loss of the bile ducts inside the liver and a narrowing of the bile ducts outside the liver within the first year of life. This leads to a buildup of bile in the liver since it cannot flow from the liver properly. Bile is a fluid that aids in digestion and is usually stored in the gallbladder, but when bile builds-up in the liver it causes liver damage. Alagille syndrome affects other organs, including the heart, eyes, spine and kidneys, and other parts of the body as well.

Causes

Alagille syndrome is genetic, meaning it is passed from parent to child. A parent with the syndrome has a 50% chance of passing the abnormal gene causing the disease on to each child. Sometimes a child has a newly developed gene abnormality and did not inherit the disease from a parent.

Symptoms

Babies born with Alagille syndrome will experience jaundice (a yellowing of the skin), pale, loose stools, and poor growth. Jaundice will improve in the first few years of life as bile flow improves. Jaundice can cause severe itching. Children with Alagille syndrome are often shorter than their peers even when they receive adequate nutrition. Other common symptoms that lead to a diagnosis of Alagille syndrome may include:

• Pulmonic Stenosis – a narrowing of the pulmonary artery, the vessel which leads from the heart to the lungs; causes a heart murmur
• Characteristic Facial Appearance – typically deep, wide-set eyes, a round forehead and a pointed chin; may not be apparent until later in life
• Posterior Embryotoxon – ring around the eye's cornea is thicker than normal; does not cause vision problems
• Kidney Problems – presence of kidney cysts or a mild kidney problem called renal tubular acidosis, where the body fails to eliminate acid adequately
• Skeletal Malformation – spinal bones may be shaped as the wings of butterfly; this “butterfly vertebrae" is usually only observed on x-ray and does not typically cause problems with spinal cord function
• Pancreatic Insufficiency – effects about one-third of children with the syndrome; pancreas does not make enough enzymes for food digestion; can lead to diarrhea
• Cholesterol Deposits – appear on the skin; result of poor flow of bile salts, which in turn affect the body's metabolism of cholesterol

Exams and Tests

Your child's pediatric gastroenterologist will diagnose Alagille syndrome based on tests and physical examination. If your baby has jaundice along with some or all of the other common symptoms, the doctor will want to do further testing.

Blood Tests

• Since the Alagille gene has been identified, a blood test for both parent and child can be done if the syndrome is suspected. The test is not perfect, however.
• A liver function test is done to assess the general state of the liver and bile duct system. Depending on the results of this test, your child's pediatric gastroenterologist may want to do a liver biopsy (tissue sample).

Biopsy

A liver biopsy is done to examine the bile ducts and the degree of scarring in the liver caused from bile buildup. Your child will receive sedation medications or a general anesthetic before the biopsy. These medications will prevent your child from feeling pain or anxiety or remembering the procedure. An area on the right side of your child's abdomen or mid-upper abdomen will be cleansed with an antibacterial soap. The biopsy site will then be numbed with an injection of lidocaine (numbing medicine). The pediatric GI specialist will insert a needle through the skin and into the liver to obtain a very small piece of liver tissue. The sample will be sent to a lab and analyzed. The doctor will apply a small pressure dressing (bandage) to the site.

After the biopsy your child will stay in or return to his/her room for four hours, when a repeat blood count is checked. (Children less than one year are observed overnight.) He or she should lie on the right side or back, depending on the biopsy site, for two hours. Being in bed will reduce the chance of bleeding after the biopsy. Once your child is awake and alert, he/she will be allowed to drink fluids. If fluids are tolerated, a regular diet can be restarted. For the remainder of the day, your child will need to participate in quiet activity. The results of the liver biopsy are usually available two weeks after the procedure.

Treatment

There is no cure for Alagille syndrome, but rather treatment to improve bile flow and to address specific symptoms.

Medication

Your child's pediatric gastroenterologist will prescribe medications to help increase bile flow. Children who experience itching as a result of long-term jaundice will be treated with medicines as well.

Nutrition

Poor bile flow leads to poor absorption of fat, resulting in poor or slow growth. Children with Alagille syndrome have striking deficiencies in vitamin A, D, E and K and require supplementation of these vitamins, sometimes in doses that are 20 times what normal babies require. Your pediatric GI specialist will monitor levels of these vitamins carefully to avoid vitamin deficiency or overdosing.

A certain type of fat called medium-chain triglycerides (MCT) is absorbed well in children with Alagille syndrome. Babies are usually prescribed a special formula that contains a high concentration of MCT. Breast-fed babies can supplement with MCT oil.

Liver Transplantation

About 20% of patients with Alagille syndrome eventually require liver transplantation due to cirrhosis (scarring) of the liver.

Points to Remember

• Alagille syndrome is usually inherited. If the disease runs in your family, you may want to consider genetic testing.
• The liver's bile duct system does not work properly, resulting in a buildup of bile in the liver.
• Many children with Alagille syndrome have other symptoms affecting the eyes, spinal cord, heart and kidneys and may have specific facial characteristics, all of which help to diagnose the disease.
• Alagille syndrome is treated with medications and nutrition supplementation.

For More Information

Alagille Syndrome Alliance - alagille.org

American Liver Foundation - liverfoundation.org

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition - NASPGHAN.org

The Childhood Liver Disease and Education Network - childrennetwork.org

U.S. National Library of Medicine - ghr.nlm.nih.gov/condition=alagillesyndrome