Alagille Syndrome Conditions and Treatments

With Alagille syndrome, children can have few to no symptoms, or they can experience multiple symptoms throughout their body, each demanding its own treatment.

Liver conditions

• Bile duct paucity. This is a hallmark feature in Alagille syndrome. Children lack enough bile ducts (tubes) in the liver to drain bile, a fluid that is made and released by the liver, into the small intestine, where it helps the intestine to digest food and absorb vitamins. When bile can’t drain easily from the liver, it backs up into the liver, causing irritation and scars.

• Cholestasis. This is a state of blocked or slowed bile flow from the liver that is caused by one of several conditions, including Alagille syndrome. Cholestasis can result in severe itching, difficulty absorbing vitamins or nutrients, poor growth, light-colored stools, and/or dark urine.

• Liver failure and end-stage liver disease. The liver is one of the only organs in the body that can regenerate itself, but sometimes the liver can become too scarred or damaged for self-repair. When this occurs, the liver isn’t working well enough to perform its necessary functions, and your child may need a liver transplant.

Liver treatments

In approximately 90 percent of children with Alagille syndrome, bile ducts (tubes) in the liver do not form or work correctly. As a result, bile (a fluid that aids digestion and carries waste) can get stuck in the liver and create scars.

• Medicines. A number of medicines can help support your child’s liver by increasing the flow of bile and the absorption of nutrients, among other benefits. Other medications can help ease pruritus (itching). No medication can treat the lack of bile ducts or grow new ones.

• Liver transplant. Sometimes a child’s liver is too scarred and damaged to function adequately, making liver transplant necessary. To determine the best time to perform a transplant, our nationally recognized liver transplant team conducts a transplant evaluation that involves blood work, imaging, and a liver biopsy, in which a tissue sample is taken from your child’s liver to measure scarring. If a transplant is needed, we place your child on the transplant waiting list maintained by United Network for Organ Sharing (UNOS). For children who have significant cholestasis (jaundice) as infants, approximately 45 percent will need a liver transplant by the time they are 18 years old. Stanford Medicine Children’s Health’s liver transplant team is one of the busiest in the nation, and our three-year liver graft patient survival rates are the best in the country.

Heart and lung conditions

Nearly 90 percent of children with Alagille syndrome are born with an abnormality of the heart or blood vessels. While it may be a simple heart problem requiring only observation, the majority of children with Alagille syndrome will likely need highly complex surgery.

• Pulmonary artery stenosis. The most common abnormality, occurring in approximately one-third of children with Alagille syndrome, is a narrowing in one or both pulmonary arteries (vessels that take blood from the heart to the lungs to gather oxygen). Depending on the severity of the narrowing and its effects on the heart, doctors will decide whether intervention is required.

• Tetralogy of Fallot (ToF). A combination of heart defects including, among other things, pulmonary stenosis (narrowing of the valve between the heart and the lungs) and a ventricular septal defect (a hole between the two lower chambers of the heart). This occurs in approximately 10 to 15 percent of children with Alagille syndrome. A ventricular septal defect can also occur as an isolated problem without pulmonary stenosis. Tetralogy of Fallot may occur as a particularly complicated form with pulmonary atresia (the pulmonary valve does not form correctly and cannot open) and major aortopulmonary collaterals (MAPCAs). In patients with MAPCAs, the pulmonary arteries do not form correctly, and the blood vessels that should connect the heart to the lungs instead bypass the heart and connect the aorta to the lungs. The blood vessels to the lungs from the heart usually look like a tree, but in this case, individual tree branches come from the aorta to send blood to parts of the lungs.

• Other congenital heart defects. These may include various holes in the heart (atrial septal defect, ventricular septal defect) and blockages in valves (pulmonary stenosis or aortic stenosis) or narrowing of blood vessels (coarctation of the aorta) that prevent blood from traveling easily from one place to the next. If left untreated, these may lead to heart failure or arrhythmias.

Heart and lung treatments

• Medicines. We may use medicines as a first step to control symptoms and improve your child’s heart function. Congenital heart disease in children with Alagille syndrome, however, often requires surgery.

• Interventional heart catheterization. If your child is experiencing problems with his or her heart or arteries, we may perform an interventional heart catheterization. In this minimally invasive procedure, a thin flexible tube, or catheter, is inserted into a main artery or vein, then advanced to the heart or lungs. A pediatric interventional cardiologist uses the catheter to insert special devices, allowing for repair of your child’s heart condition. In this way, the cardiologist may be able to repair holes in the heart, fix malformed blood vessels, and/or widen narrowed blood vessels.

• Heart surgery. Some children with Alagille syndrome may require complex, intricate heart surgery. When surgery is needed, our highly skilled cardiologists with a subspecialty in Alagille syndrome team up with our world-renowned cardiothoracic surgeons to provide exceptional care with outstanding outcomes for your child. When the pulmonary arteries are stenosed (narrowed), pulmonary artery reconstruction may be necessary. Our Pulmonary Artery Reconstruction (PAR) program is the top program in the world for these highly technical procedures. In cases of pulmonary artery stenosis, careful attention to each area of narrowing allows for improved blood flow and lowering of the blood pressure and workload of the heart. In patients with MAPCAs, the PAR program is famous for a novel, highly complex technique called unifocalization, developed and pioneered by our Children’s Heart Center director, Frank L. Hanley, MD. Pediatric patients from all over the world travel to Lucile Packard Children’s Hospital Stanford to receive this lifesaving surgery from Dr. Hanley and his team. Unifocalization brings together each of the individual blood vessels (branches) arising from the aorta to form a complete tree of blood vessels directly from the heart to the lungs.

Other conditions related to Alagille syndrome

Sometimes the kidneys, blood vessels of the brain or body, gastrointestinal tract, bones, and eyes also require specific attention and subspecialty care. Babies with moderate to severe Alagille syndrome can also “fail to thrive,” meaning they do not grow and develop as well as their peers. For all these conditions, we collaborate closely with experts in each specialty, including pediatric neurosurgeons, neurologists, nephrologists, endocrinologists, gastroenterologists, geneticists, and ophthalmologists at Stanford Medicine Children’s Health. They become a part of your child’s care team and help guide treatment decisions.

• Kidney conditions may include smaller-than-average kidneys and renal tubular acidosis (the kidneys can’t process acid correctly). About four out of 10 children with Alagille syndrome have a kidney condition.

• Esophageal varices (swollen or enlarged veins) occur when the liver becomes very congested from scarring, and blood has trouble flowing easily back to the heart, creating back pressure and swelling. This may cause bleeding from the varices in the lower esophagus (the connection between the mouth and stomach). When varices become very large, they are at high risk of bleeding. Our team may perform a procedure called an upper endoscopy (camera exam via the mouth under anesthesia) to evaluate and potentially treat these varices.

• Vascular malformations in the brain can be seen in about 40 percent of children with Alagille syndrome. These malformed blood vessels may go unnoticed until they cause bleeding within the skull and become life-threatening. As a precaution, we perform a specialized Alagille syndrome magnetic resonance imaging (MRI) on all children in our program once they reach a certain age to detect these potentially asymptomatic findings early. When a malformation is noticed, such as moyamoya disease (weak blood vessels in the brain or blocked arteries at the base of the brain), our world-renowned neurosurgeon performs cerebral vascular surgery to restore blood flow in your child’s brain.

• Abdominal vascular malformations can be found in about 30 percent of children and also often occur without symptoms. Our standardized imaging protocol has been designed to catch these abnormalities early as well.

• Problems with eyes involving the cornea, iris, and pupil are fairly common but not often clinically significant.