Alagille syndrome is a rare genetic or inherited disorder, which causes a person to have less than normal number of small bile ducts inside the liver. Bile ducts are small tubes that carry bile from the liver cells to the gall bladder where it is stored. Bile is eventually drained into the small intestine when the need arises.
Functions of bile include carrying toxins and other waste products out of the body and helping in the digestion of fats and fat-soluble vitamins (A, D, E, and K). The decreased number of bile ducts—also called hepatic ducts—causes bile to build up in the liver. Liver damage can result from this excessive build up. Progressive liver damage can lead to liver failure, thus, the need for liver transplantation.
Alagille syndrome can also affect other parts of the body. Organs affected by the condition may include the heart, blood vessels, kidneys, spleen, skeleton, eyes, and face.
Alagille Syndrome Causes
Alagille syndrome is an inherited disorder. It is an autosomal dominant disorder, which means it can be inherited from one parent who has the disorder. If a child has a parent with Alagille syndrome, he or she has a 50 percent chance of developing the condition. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), most people with Alagille syndrome have a defect, or mutation, in their gene, called Jagged 1 (JAG1). In some, less than 1 percent of people with Alagille syndrome, mutations in NOTCH 2 gene are seen.
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Symptoms
Symptoms of Alagille syndrome and their severity may vary from person to person. In addition, symptoms depend on what organ is affected.
Because the symptoms of Alagille syndrome vary and because the syndrome is so rare, the disorder can be difficult to diagnose. The doctor may use the following to make a diagnosis:
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Treatment
Treatment for Alagille syndrome is aimed at increasing the flow of bile from the liver, promoting growth and development, and making the person as comfortable as possible. Other treatments address specific symptoms of the disease.
Pruritus. Itching may improve when the flow of bile from the liver is increased. Medications may be prescribed to relieve pruritus. Hydrating the skin with moisturizers and keeping fingernails trimmed to prevent skin damage from scratching are important.
If severe pruritus does not improve with medication, a procedure called partial external biliary diversion (PEBD) may provide relief from itching. PEBD involves surgery to connect one end of the small intestine to the gallbladder and the other end to an opening in the abdomen—called a stoma—through which bile leaves the body and is collected in a pouch.
A liver transplant may be necessary for a person with liver failure and severe pruritus that does not improve with medication or PEBD.
Malabsorption and growth problems. Infants with Alagille syndrome are given a special formula that allows the absorption of much-needed fat by the small intestine. Infants, children, and adults can benefit from a high-calorie diet, calcium, and vitamins A, D, E, and K. If oral doses of vitamins are not well tolerated, a health care provider may need to give the person injections for a period of time. A child may receive additional calories through a tiny tube that is passed through the nose into the stomach. If extra calories are required for a long time, a tube, called a gastrostomy tube, may be placed directly into the stomach through a small opening made in the abdomen. The child’s growth may improve if nutrition status improves and the flow of bile from the liver increases.
Xanthomas. These fatty deposits typically worsen over the first few years of life and then improve over time, or they may eventually disappear in response to PEBD or the medications used to increase bile flow.
Liver failure. In some cases, Alagille syndrome will progress to end-stage liver failure and require a liver transplant. A liver transplant is when the diseased liver is removed and replaced with a healthy one from an organ donor.
The health care team carefully considers the risks and benefits of a transplant and discusses them with the patient and family. People with Alagille syndrome and heart problems may not be candidates for a transplant because they could be at high risk for complications during and after the procedure.
Source: Adapted from the National Digestive Diseases Information Clearinghouse (NDDIC). Alagille Syndrome. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health. NIH Publication No. 09–6408, February 2009
Page Last Revised: February 7, 2012
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Functions of bile include carrying toxins and other waste products out of the body and helping in the digestion of fats and fat-soluble vitamins (A, D, E, and K). The decreased number of bile ducts—also called hepatic ducts—causes bile to build up in the liver. Liver damage can result from this excessive build up. Progressive liver damage can lead to liver failure, thus, the need for liver transplantation.
Alagille syndrome can also affect other parts of the body. Organs affected by the condition may include the heart, blood vessels, kidneys, spleen, skeleton, eyes, and face.
Alagille Syndrome Causes
Alagille syndrome is an inherited disorder. It is an autosomal dominant disorder, which means it can be inherited from one parent who has the disorder. If a child has a parent with Alagille syndrome, he or she has a 50 percent chance of developing the condition. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), most people with Alagille syndrome have a defect, or mutation, in their gene, called Jagged 1 (JAG1). In some, less than 1 percent of people with Alagille syndrome, mutations in NOTCH 2 gene are seen.
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Symptoms
Symptoms of Alagille syndrome and their severity may vary from person to person. In addition, symptoms depend on what organ is affected.
Liver Symptoms[Top of Page]
Infants with Alagille syndrome may have symptoms of liver disease and poor bile drainage from the liver in the first few weeks of life. These symptoms can also occur in children and adults with Alagille syndrome.
Jaundice.
Bilirubin is the pigment that gives bile its reddish-yellow color. Jaundice occurs when the bilirubin content in the blood rises, causing yellowing of the skin and whites of the eyes. High levels of bilirubin in the blood can darken the urine, while stools may become pale, gray, or white from a lack of bilirubin in the intestines.
Many healthy newborns have mild jaundice due to immaturity of the liver. This type of jaundice disappears by the second or third week of life, whereas the jaundice of Alagille syndrome remains. Infants with jaundice that persists should be checked by a doctor.
Pruritus.
The buildup of bilirubin in the blood may cause itching, also called pruritus. Pruritus usually starts after 3 months of age and can be severe.
Malabsorption and growth problems. People with Alagille syndrome may have diarrhea because of malabsorption, a condition in which the bowel does not properly absorb fats and fat-soluble vitamins. Malabsorption occurs because bile is necessary for their digestion. Malabsorption can lead to failure to thrive in infants and poor growth and delayed puberty in older children. People with Alagille syndrome and malabsorption may develop bone fractures, eye problems, blood-clotting problems, and learning delays.
Xanthomas.
Xanthomas are fatty deposits that appear as yellow bumps on the skin. They are caused by abnormally high cholesterol levels in the blood, which is common in people with liver disease. Xanthomas are found on the abdomen, knees, elbows, hands, and around the eyes and are harmless.
Unique SymptomsDiagnosis
Alagille syndrome can affect other parts of the body in ways that may help doctors distinguish it from other liver conditions.
Heart. A heart murmur is the most common sign of Alagille syndrome other than liver disease. Most people with Alagille syndrome have a narrowing of the pulmonary arteries, which carry blood from the heart to the lungs. This narrowing causes a murmur that can be heard with a stethoscope, but usually it does not cause problems. A small number of people with Alagille syndrome have more serious heart conditions involving problems with the walls or the valves in the heart. The more serious conditions may require medications and corrective surgery.
Face. Many children with Alagille syndrome have deep-set eyes; a straight nose; a small, pointed chin; and a prominent, wide forehead. These features are not usually recognized until after infancy. The face typically changes with age, and by adulthood the chin is more prominent.
Eyes. Posterior embryotoxon is a condition in which an opaque ring is seen in the cornea, the transparent covering of the eyeball. A specialist performs an eye examination, called the slit lamp test, to look for the condition. The abnormality is common in people with Alagille syndrome and usually does not affect vision.
Skeleton. The shape of the bones of the spine may look abnormal on an x ray, but this abnormality rarely causes spine problems.
Kidneys. A wide range of kidney diseases can occur in Alagille syndrome. Some people have small kidneys or cysts in the kidneys. The kidneys can also have decreased function.
Spleen. The spleen is a small abdominal organ that cleans blood and protects against infection. Blood flow from the spleen drains directly into the liver. When liver disease is advanced, the blood flow backs up into the spleen and other blood vessels. This condition is called portal hypertension. The spleen may enlarge in the later stages of liver disease. A person with an enlarged spleen should avoid contact sports to protect the organ from injury.
Blood vessels. People with Alagille syndrome may have abnormalities of the carotid arteries—the blood vessels in the head and neck. This serious complication can lead to internal bleeding or stroke. If a person with Alagille syndrome suffers a head injury, prompt evaluation and magnetic resonance imaging (MRI) or a computerized tomography (CT) scan of the brain are needed to check for problems. Alagille syndrome can also cause narrowing or bulging of other blood vessels in the body.
Because the symptoms of Alagille syndrome vary and because the syndrome is so rare, the disorder can be difficult to diagnose. The doctor may use the following to make a diagnosis:
evaluation of the symptoms of Alagille syndromeYour doctor may also recommend imaging tests, such as ultrasound and other diagnostic procedures to check for other abnormalities.
liver function tests
a liver biopsy
a blood test to look for a JAG1 gene mutation
genetic workup
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Treatment
Treatment for Alagille syndrome is aimed at increasing the flow of bile from the liver, promoting growth and development, and making the person as comfortable as possible. Other treatments address specific symptoms of the disease.
Pruritus. Itching may improve when the flow of bile from the liver is increased. Medications may be prescribed to relieve pruritus. Hydrating the skin with moisturizers and keeping fingernails trimmed to prevent skin damage from scratching are important.
If severe pruritus does not improve with medication, a procedure called partial external biliary diversion (PEBD) may provide relief from itching. PEBD involves surgery to connect one end of the small intestine to the gallbladder and the other end to an opening in the abdomen—called a stoma—through which bile leaves the body and is collected in a pouch.
A liver transplant may be necessary for a person with liver failure and severe pruritus that does not improve with medication or PEBD.
Malabsorption and growth problems. Infants with Alagille syndrome are given a special formula that allows the absorption of much-needed fat by the small intestine. Infants, children, and adults can benefit from a high-calorie diet, calcium, and vitamins A, D, E, and K. If oral doses of vitamins are not well tolerated, a health care provider may need to give the person injections for a period of time. A child may receive additional calories through a tiny tube that is passed through the nose into the stomach. If extra calories are required for a long time, a tube, called a gastrostomy tube, may be placed directly into the stomach through a small opening made in the abdomen. The child’s growth may improve if nutrition status improves and the flow of bile from the liver increases.
Xanthomas. These fatty deposits typically worsen over the first few years of life and then improve over time, or they may eventually disappear in response to PEBD or the medications used to increase bile flow.
Liver failure. In some cases, Alagille syndrome will progress to end-stage liver failure and require a liver transplant. A liver transplant is when the diseased liver is removed and replaced with a healthy one from an organ donor.
The health care team carefully considers the risks and benefits of a transplant and discusses them with the patient and family. People with Alagille syndrome and heart problems may not be candidates for a transplant because they could be at high risk for complications during and after the procedure.
Source: Adapted from the National Digestive Diseases Information Clearinghouse (NDDIC). Alagille Syndrome. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health. NIH Publication No. 09–6408, February 2009
Page Last Revised: February 7, 2012
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