Alagille syndrome is a rare, inherited disorder that can affect the liver. The heart, eyes, bones, kidneys and nervous system may be affected as well. This disorder is present at birth, but some of the clinical features may not become apparent until later in life.

Patients with Alagille syndrome may have fewer than normal bile ducts in the liver. This causes a decrease in the flow of bile out of the liver which leads to reduced digestion of dietary fat and vitamins (A, D, E, K). The key clinical features are poor growth, itching, and progressive liver injury.

There is no specific treatment for Alagille syndrome. Management of the condition is aimed at preventing and monitoring for complications. This can include increasing the flow of bile from the liver, maintaining normal growth and development, and reducing the degree of itching. Most people with Alagille syndrome can manage their condition through medication or nutrition therapies.

About 15 percent of people with Alagille syndrome will develop cirrhosis (severe damage to the liver). Liver transplantation is the only option for these patients. They will need a liver from a deceased donor or a segment of a liver from a living donor. Both types of transplants are available from the expert liver transplant team at Cincinnati Children’s.

Causes of Alagille Syndrome

The disease usually is inherited from one parent. A single copy of the changed gene (received from either the mother or father) "dominates" the unchanged gene and results in this disease.

There is a 50% chance a parent with Alagille syndrome will transfer this disorder to their child. Family members with Alagille syndrome may be affected differently by the disorder.

Signs and Symptoms of Alagille Syndrome

Bile, composed of bilirubin, bile salts, cholesterol and metals such as copper, is produced in the liver. It travels through small bile ducts in the liver into one large bile duct. It eventually flows into the intestines. Bile acids are necessary to absorb fat and certain vitamins. When the bile flow is decreased, each of its parts build up in the body. The body is not able to properly absorb fat and vitamins. This causes a wide range of symptoms.

Symptoms of liver disease in subjects with Alagille syndrome range from mild to severe. Symptoms within the first three months of life often include:

• Jaundice (yellowing of skin), usually present at birth
• Severe itching
• Pale, loose or clay-colored stools. This happens because there is little or no bile reaching the intestine to color the bowel movements.
• Poor weight gain due to a lack of bile needed to digest and absorb fat.
• Poor growth
• Deficiency of vitamins A, D, E and K, which depend on bile acids for digestion / absorption. This may result in vision changes, rickets, difficulty with balance and poor clotting of the blood.

Other liver-related symptoms that may develop later include:

• Enlarged liver that feels larger and harder than normal.
• Hard, white / yellow nodules (called xanthomas) that develop in the skin due to cholesterol and fatty deposits. The nodules usually occur on the knees and elbows.

Diagnosis of Alagille Syndrome

A diagnosis of Alagille syndrome may be made based on clinical features and confirmed by genetic testing. There are specific findings that indicate Alagille syndrome, but your child may not have all the symptoms.

A liver biopsy may be done to look at the bile ducts and amount of scarring in the liver. Blood tests are used to assess the general state of the liver.

Genetic testing is being used more often to identify abnormal genes associated with Alagille syndrome.

Other findings that may indicate Alagille syndrome include:

• Heart murmur due to narrowing of the blood vessel connecting the heart to the lungs.
• Bone defects where the shape of the bones in the spinal column has a “butterfly wing”-like appearance.
• Kidney problems or kidney failure
• Distinct physical features, such as a broad forehead, straight nose, deep set eyes, a small, pointed chin, and fingers that are shorter than normal.
• Problems with the eye called a posterior embryotoxon. This is a thickening of the Schwalbe's line, on the surface of the eye.

Treatment for Alagille Syndrome

Medications. Medicine may be used to increase bile flow and may relieve severe itching. These same medicines may be used to treat high cholesterol levels that cause the hard, whitish nodules that develop

Vitamin supplements. Fat-soluble vitamin supplements (A, D, E and K) may be used due to difficulty digesting/absorbing dietary fat and vitamins.

Nutritional supplements. Baby formula rich in a type of fat that can be digested despite reduced bile flow may be used to help with fat absorption in infants.

High-calorie diet. To prevent malnutrition and growth failure, a high-calorie diet with added protein may be recommended. A feeding tube that delivers large quantities of nutrients overnight may be recommended.

Liver transplantation. Patients who develop cirrhosis (severe damage to the liver) will need a liver transplant.

This may be considered for subjects with portal hypertension (caused by excessive scarring in the liver) and severe growth failure that are not responding to medication. Liver transplantation has been used successfully in these cases.

Cincinnati Children’s has one of the largest and oldest pediatric liver transplant programs in the United States Cincinnati Children’s patients experience shorter average times on the transplant waitlist.

• The median wait time for a new liver at Cincinnati Children’s is 3.7 months, compared to the national median wait time of 8.7 months.
• 66.2% of our patients receive a transplant within one year of wait listing, compared to 49.3% nationally.

Long-Term Outlook

Early diagnosis and treatment can help people with Alagille syndrome live longer, more comfortable lives.

Prognosis depends on the severity of the bile flow obstruction and scarring of the liver, and the severity of other problems that may develop. This may include heart, kidney, or nervous system problems.

Children with Alagille syndrome usually have a better outcome than children with other liver disorders at the same age. Many adults with Alagille syndrome lead normal lives.