Children's Hospital Colorado

Alagille Syndrome

What is Alagille syndrome?

Alagille syndrome is a genetic disorder, meaning that it is caused by a missing or mutated piece of deoxyribonucleic acid (DNA). DNA is the substance that makes up our genetic code, which provides the body with a blueprint for how to develop and function.

Specifically, Alagille syndrome is caused by the deletion or mutation of the JAG1 or NOTCH2 gene, which results in the body forming an insufficient number of bile ducts in the liver. Bile is the substance the body makes to help remove waste; when the body does not have enough bile ducts, bile can back up in the liver, causing liver disease and other complications.

In addition to a low number of bile ducts, we also associate Alagille syndrome with these conditions:

  • Unique facial structure
  • Heart abnormalities
  • Butterfly-shaped vertebrae
  • Kidney abnormalities
  • Blood vessel abnormalities
  • Posterior embryotoxon (an abnormally thick line bordering the eye’s iris)
  • Short stature

Who gets Alagille syndrome?

About 40% of newborns with Alagille syndrome have inherited it from a parent, while about 60% are born with a gene mutation that was not passed down from either parent. Alagille syndrome affects boys and girls of all races the same. It occurs in about one out of every 30,000 live births.

Children with Alagille syndrome show a variety of symptoms, many of which are related to the underperforming liver:

  • Jaundice (yellow-colored skin)
  • Icterus (yellow-colored eyes)
  • Itching, bleeding and bruising easily
  • Below-average growth
  • Vitamin deficiencies

We also associate these other symptoms with Alagille syndrome that are not linked to the liver:

  • Heart murmurs
  • Kidney abnormalities
  • Triangular-shaped face, which includes characteristics like a prominent forehead, deep-set eyes, a pointed chin and a bulbous (round or bulging) nose

What tests are used to diagnose Alagille syndrome?

If your child shows symptoms of Alagille syndrome, doctors at Children's Hospital Colorado will perform several tests to diagnose it:

  • Liver biopsy: By removing a small piece of the liver and examining it under a microscope, we can tell if the liver has the standard number of bile ducts.
  • Echocardiogram: By using an ultrasound, which shows us an image using sound waves, we can see if the heart has any abnormalities.
  • Eye exam: Performing a close inspection of the eye allows us to identify posterior embryotoxon, which is a condition that makes the line bordering the iris thicker and asymmetrical.
  • X-ray: By using a small amount of radiation to produce an image of the spine, an X-ray can show us if the vertebrae resemble a butterfly shape.
  • Genetic testing: Ultimately, we make a final diagnosis for Alagille syndrome by performing a genetic test to see if specific genes are mutated or missing.

Why choose us for Alagille testing?

Because of the wide variety of symptoms associated with Alagille syndrome, it can be difficult to diagnose. At Children's Colorado, we have a team that includes many different specialists who work together to quickly obtain all the test results required to diagnose Alagille syndrome.

Because the syndrome directly affects the liver, it is important to not only have a doctor who specializes in the liver (called a hepatologist), but also one who specializes in children's livers.

Here's what you can expect at Children's Colorado:

  • Our liver biopsies are performed by a board-certified pediatric hepatologist.
  • Our hepatologist works with a pediatric anesthesiologist, who knows just the right amount of anesthesia to give a child if they need to be put to sleep for a procedure.
  • Our board-certified pediatric pathologist has extensive experience looking at children’s liver tissue under a microscope, so they know exactly what to look for and how a child's liver differs from an adult's liver.

How is Alagille syndrome treated?

Children with Alagille syndrome require a special diet and vitamins to help reduce the amount of bile their liver produces. We can also prescribe medicine to help if your child is experiencing itching or bleeding from their gastrointestinal tract. About 20 to 30% of children with Alagille syndrome will require a liver transplant.

The reason for a liver transplant is because Alagille syndrome causes complications that eventually make the liver ineffective. Alagille syndrome can lead to cholestasis, which is an elevated level of bilirubin (an orange-yellow pigment made in the liver to breakdown hemoglobin). It can also cause itching that does not respond to medication, failure of the liver to grow and scarring or cirrhosis of the liver. These conditions often do not respond to treatment, which is why a liver transplant may ultimately be necessary.

Why choose us for treatment of Alagille syndrome?

The Pediatric Liver Center at Children's Colorado has extensive experience caring for children with Alagille syndrome. Our multidisciplinary team can address the complications of the liver, heart, kidney, nutrition and bones that are associated with Alagille syndrome. We not only provide diagnostic testing and care, but also genetic counseling, referrals to specialists and long-term care.

Our hepatology team conducts research on Alagille syndrome and is currently evaluating new medications to address the problem of constant itching.

While most children with Alagille syndrome do not require a liver transplant, our team is ready if it becomes necessary. We have experienced doctors and surgeons who specialize in the transplant care of children with Alagille syndrome. In addition to deceased donor transplants, we also have a robust live donor liver transplant program. Colorado is known for its short waitlist times and Children's Colorado allows patients to be multi-listed at more than one transplant center in the country.

The Transplant Program at Children's Colorado is known for its exceptional patient and graft survival outcomes.

Genetics Home Reference is part of the U.S. National Library of Medicine and provides consumer-friendly information about the effects of genetic variation on human health, including Alagille syndrome.

The National Institute of Diabetes and Digestive and Kidney Diseases conducts research that creates knowledge about and treatments for diseases that are among the most chronic, costly and consequential for patients, their families and the Nation.