Alagille Syndrome

What Causes Alagille Syndrome?

In most cases, it is caused by a problem or missing section of a gene called JAG1. In some rarer cases, it is caused by a change in the NOTCH2 gene or an unknown problem. This happens during fetal development, before the baby is born. It can be passed along from a parent (inherited), or it can happen by chance. JAG1 and NOTCH2 genes give directions to make proteins that help cells communicate and send signals that are important to develop various parts in the body.

What Are Signs and Symptoms of Alagille Syndrome?

Most people with Alagille syndrome are diagnosed as babies or young children. Symptoms can vary from very mild to severe. Signs and symptoms of Alagille syndrome include:

• Certain facial features. These include a wide forehead and small, pointed chin. This can make the face look almost triangular. The eyes may also be deep-set or far apart.
• Yellowish skin and eyes (jaundice). This is caused as bile builds up in the liver due to having too few, very small or misshaped bile ducts in the liver.
• Problems with nutrition and growth. When the liver can’t get bile to the intestines, people can’t digest fat well. This can lead to trouble gaining weight, pale and/or loose stools and vitamin deficiencies. Vitamin deficiencies can have their own symptoms, such as poor bone development, trouble with vision or balance and more.
• Constant itching. The buildup of bile in the liver can also cause a strong feeling of itchiness that can sometimes result in intense scratching.
• Heart problems. Many people with Alagille syndrome have narrower blood vessels connecting the heart to the lungs. This can cause a harmless murmur or a serious problem pumping blood. In severe cases, children may require heart surgery to fix the problem.
• Problems with blood vessels. As in the heart, blood vessels in the head and neck can also be too narrow or malformed. This can increase the risk of stroke or other problems.
• Problems with the kidneys. Sometimes the kidneys don’t work as well because they are small or have cysts or other problems.
• Enlarged spleen. When the liver doesn’t work well, extra blood may fill up the spleen, causing swelling.
• White or yellow skin bumps. These bumps, called xanthomas, often show up on the knees, elbows, other joints, hands and feet. They are caused by a buildup of fat (cholesterol) and can also be a sign of liver not working optimally.
• Changes to spine bones and the eyes. Although most patients have no symptoms from these changes, bones in the spine may have a butterfly shape. Most patients also have a change called posterior embryotoxon, a harmless white ring around the eye that can be seen in an eye exam.

How Is Alagille Syndrome Diagnosed?

Diagnosis is made by a combination of a thorough medical history, physical signs and symptoms, blood and genetic testing, imaging and a liver biopsy.

If your child’s doctor suspects Alagille syndrome, they may offer genetic testing, done through a simple blood test. Your child will also have a thorough health check that will involve questions about their medical history and your family's medical history.

The health care team will check your child’s eyes, spine, belly and organs such as the heart, liver, kidneys, spleen, pancreas and brain. This will involve a physical check, specific blood tests, imaging of different organs, and a liver biopsy.

Liver tests such as a liver biopsy (tissue sample) and liver imaging are usually done to check for anomalies in the number or shape of the bile ducts. If these are found, Alagille syndrome will be diagnosed if a person also has other organs involved. Genetic testing can be used to confirm is a mutation is present.

How Is Alagille Syndrome Managed?

Management mainly supports and treats symptoms, focusing on affected organ systems. Liver transplantation might be needed for severe liver disease, intense itching that doesn't respond to treatment or growth issues.

Some people with Alagille syndrome have few or no symptoms and may not need treatment. In other cases, people can manage the condition with changes in diet or by taking certain vitamins.

Usually, Alagille syndrome diet changes involve a high-fat, high-calorie diet. This is because people with Alagille syndrome often don’t take in (absorb) all of the nutrients from the food they eat. They must get extra nutrients to have enough to grow and maintain their health.

In people with more symptoms, including some liver problems, management may include:

• Medicine to help the liver move more bile through
• Medicine and lotions to help soothe itchy skin
• High-calorie baby formula or food supplements (in some cases, children may need a feeding tube at night to help them get enough calories)
• Vitamins (especially A, D, E and K)
• Surgery to correct problems with the heart blood vessels or poor bile drainage in the liver

About 15% of patients with Alagille syndrome end up with liver failure due to the condition. In these cases, a liver transplant can help with many symptoms and can be life-changing. It improves quality of life and resolves symptoms associated with bile accumulation and poor liver function such as extreme itching and nutrition difficulties, but it does not cure the primary genetic defect or reverse all growth parameters or address other systemic complications of Alagille.

What to Expect When Living With Alagille Syndrome

Many people with Alagille syndrome live fairly normal lives. Even people with health problems from the disease can often manage them well. In these cases, lifestyle and diet changes can help slow liver damage and improve growth. Long, active, happy lives are possible!

Treatment needs and health impacts will change over time. Families who have a child with Alagille syndrome can expect:

• Regular doctor visits, sometimes with more than one specialist
• Regular blood, heart, liver and nutrition tests
• Growth checks for height and weight
• Special diets and possible night-time feeding tubes

Because of problems with the liver, spleen and blood vessels, people with Alagille syndrome may be more prone to certain injuries. For example, they may break bones more easily or have a swollen spleen that can burst during sports or other activities. Blood vessel problems may also make them more likely to have bleeding problems in the brain after even a minor head injury. These problems can be deadly, so many health care teams take extra care when there is an injury. They may offer brain imaging or other tests to check for bleeding or other problems.

Also, people with Alagille syndrome may not be able to take certain medicines that are hard on the liver or kidneys. Always talk to your child’s doctor before giving your child medicine, natural remedies or dietary supplements.

When Should I Seek Help for My Child?

If your child has any health symptoms that alarm you, such as difficulty breathing, trouble staying awake or lack of responsiveness, seek emergency care immediately.

If your child has symptoms of Alagille syndrome listed above (jaundice, itching, poor growth, triangular face, etc.), ask your child’s doctor about the condition. Fill out our form to speak with our team.

If you think your child may have Alagille syndrome but your child has no major symptoms, tell your child’s pediatrician. They can evaluate your child for other risk factors that may help you figure out if Alagille syndrome is an issue. You may also wish to ask about genetic testing if a family member has a recent diagnosis of Alagille syndrome.

Why Choose Nationwide Children's?

It's not just who treats your child that makes a difference at Nationwide Children's. It's how your child is treated here. Helping children feel better is our purpose and what drives the team each day. It's why we do what we do. It's the combination of patient-centered care and state-of-the-art capabilities that makes the Pancreas and Liver Care Center a truly unique environment for healing.

The Pancreas and Liver Care Center provides the complete range of treatment for children with any type of pancreas or liver problem. The team includes the nation's leading medical and surgical experts in pancreas and liver care. From imaging, advanced and interventional endoscopy, and comprehensive pain management to complex surgical procedures, the team does it all. In fact, some procedures are so advanced that Nationwide Children's is one of only a few centers in the world that has the capabilities to offer them. When your child comes to our center, you can expect:

• Comprehensive consults and care from a full team of specialists, including the nation’s leading medical and surgical pancreas and liver experts
• Personalized treatment plans designed for every child's and family's situation and health history
• Pain and nutrition management strategies that go beyond medication to improve physical function and quality of life
• Surgical management based on organ anatomy and structure, as well as genetic risk factors

Leading the Way to New Treatments and Outcomes Through Clinical Research

Clinical care and research work together. This helps scientists and doctors to find new treatments and therapies. Clinical studies (also called clinical trials) will continue to become more common in daily care at Nationwide Children's. Clinical studies help doctors learn more about conditions and treatment.

This means you might hear about a clinical study that your child might be able to join. This does not mean that your child has to join a study. You always have the choice about whether or not to join a study.

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Speak With Our Team

Families from across the United States and around the world come to the Pancreas and Liver Care Center at Nationwide Children’s Hospital for advanced clinical and surgical services, some of which are available at only a handful of centers in the world. To speak with a member of our team, please complete the following information and someone will respond to you within two business days.

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Nationwide Children’s also offers online second opinions for pancreas and liver care. If you are currently receiving care at another institution and would like a second opinion from experts at Nationwide Children’s, please visit our Online Second Opinion Program.