What is Alagille Syndrome?
Alagille syndrome is a rare, inherited disorder that can affect the liver. The heart, eyes, bones, kidneys and nervous system may also be affected. This disorder is present at birth, but some of the symptoms may not be seen until later in life.
Patients with Alagille syndrome may have fewer than normal bile ducts in the liver, which causes less bile to flow out of the liver. This causes the body to have problems digesting and absorbing needed fat and vitamins (A, D, E, K). The main symptoms are poor growth, itching, and progressive liver injury.
There is no cure for Alagille syndrome. But the condition can be managed to help prevent complications. This can include increasing the flow of bile from the liver, maintaining normal growth and development, and reducing itching. Most people with Alagille syndrome can manage their condition through medicine or nutrition therapies.
About 15% of people with Alagille syndrome will develop cirrhosis (severe damage to the liver), and they will need a liver transplant.
What Causes Alagille Syndrome?
The disease usually is inherited from one parent. A single copy of the changed gene (from either the mother or father) "dominates" the unchanged gene and causes this disease.
There is a 50% chance a parent with Alagille syndrome will transfer it to their child. Family members with Alagille syndrome may be affected differently by the disorder. If a child is diagnosed with Alagille syndrome, testing for the parents and other siblings is recommended. While the parents and siblings may have no known symptoms, it is important for them to be checked and have regular follow-ups if Alagille is diagnosed.
What are the Symptoms of Alagille Syndrome?
Bile, made up of bilirubin, bile salts, cholesterol and metals like copper, is made 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 needed to absorb fat and certain vitamins. When the bile flow is decreased, the body cannot properly absorb fat and vitamins. This causes a wide range of symptoms.
Symptoms of liver disease in people 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
- Lack of vitamins A, D, E and K, which need bile acids for digestion/absorption. This may cause vision problems, Rickets, problems with balance, and/or poor clotting of the blood.
Other liver-related symptoms that may happen later include:
- Liver that feels larger and harder than normal.
- Hard, white/yellow nodules or bumps (called xanthomas) that develop in the skin due to cholesterol and fatty deposits. The nodules usually are seen on the knees and elbows.
How is Alagille Syndrome Diagnosed?
A diagnosis of Alagille syndrome may be made based on symptoms 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 check 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 embryotoxo
How is Alagille Syndrome Treated?
Medications. Medicine may be used to increase bile flow and may lessen severe itching. These same medicines may be used to treat high cholesterol levels that cause the hard, white-ish nodules (xanthomas) to develop in the skin.
Vitamin supplements. Fat-soluble vitamin supplements (A, D, E and K) may be used to increase the chance that dietary fat and vitamins can be digested/absorbed.
Nutritional supplements. Baby formula that has a type of fat that can be digested even with reduced bile flow may be used to help with fat absorption in infants.
High-calorie diet. To prevent malnutrition and poor growth, a high-calorie diet with added protein may be used. A feeding tube that delivers nutrients overnight may be recommended.
Liver transplantation. Patients who develop cirrhosis (severe damage to the liver) will need a liver transplant.
Liver transplant may also be considered for patients with portal hypertension (caused by excessive scarring in the liver) and severe lack of growth that are not responding to medication. 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 2.5 months, compared to the national median wait time of 4.6 months.
- 73.3% of our patients receive a transplant within one year of wait listing, compared to 56.6% nationally.
Long-Term Outlook
Early diagnosis and treatment can help people with Alagille syndrome live longer, more comfortable lives.
Outlook depends on how limited the bile flow is and how much the liver is scarred, and any 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.
