Index
It affects approximately one in 30,000 live births.
Alagille syndrome is a rare genetic disease . It can affect different parts of the body, including the liver, heart, kidneys, eyes, face, and bones.
There are many different ways that Alagille syndrome can affect a person.
It is different from person to person and even two people in the same family with Alagille syndrome can have different characteristics and symptoms.
Some people have a very mild form of the condition and reach adulthood not knowing they have Alagille syndrome. Others may be sick from the time they are babies and be diagnosed at a very young age.
Alagille syndrome is a condition in which bile builds up in the liver because there are too few bile ducts to drain the bile. This results in liver damage.
The liver produces bile to help remove waste from the body. Bile helps digest fats in conjunction with fat-soluble vitamins A, D, E, and K.
The body can use these vitamins only if they are combined with the fat from the food you eat.
The bile ducts are the channels that move bile out of your liver. If you don’t have enough of these ducts, bile builds up in your liver.
This damages liver tissues and can ultimately cause liver failure.
As treatment options increase, people with this condition live longer and more comfortable lives, especially if the condition is discovered early.
A percentage that oscillates around 75% of the people who have been diagnosed with Alagille syndrome in childhood live to be 20 years old.
Causes of Alagille syndrome
The cause of Alagille syndrome is genetic. Genes are made up of DNA and act as instructions for the body. Genes determine different characteristics, such as the color of our hair and eyes.
They also control how different parts of our body develop and function.
More than nine out of ten people with Alagille syndrome have a mutation (change) in a gene called JAG1.
A very small number have a mutation in a gene called NOTCH2.
These genes are involved in many different systems in the body, so Alagille syndrome can have a wide variety of effects.
We have two copies of each gene in our body, but only one of the NOTCH2 or JAG1 genes must be affected to cause Alagille syndrome.
People can have different mutations in these genes, and more than 430 different forms of these genes have been identified.
This explains why Alagille syndrome can have severe effects in some people and milder effects in others.
In about six out of ten people with Alagille syndrome, the mutation that causes the disease is known as “sporadic.”
This means that the gene has not been passed down from the parents, but is present for an unknown reason.
In four out of ten cases, the gene that causes Alagille syndrome has been passed from a parent to their child.
Symptoms
The symptoms of Alagille syndrome usually appear in the first two years of life.
In each patient there is a particular way of experiencing the symptoms.
The following are the most common symptoms of Alagille syndrome:
Liver abnormalities
People with Alagille syndrome may have fewer bile ducts than normal. This is known as a shortage of bile ducts.
The bile ducts are responsible for transporting bile from the liver to the gallbladder and small intestine.
When there are fewer ducts to carry bile, the bile can become trapped in the liver and cause damage. This causes jaundice.
Bile is colored with a pigment called bilirubin. Some of the changes that could be seen when the liver cannot get rid of bile, related to this pigment are:
- You may have yellowish skin and yellow color on the whites of your eyes, called jaundice.
- Stools may appear pale, gray, or white due to a lack of bile.
- Urine may also appear darker in color.
- A newborn may be jaundiced for a few days or weeks until his liver works more effectively.
Skin itch
Increased bilirubin in your body can cause an itchy sensation, called pruritus.
Liver damage can cause problems such as malabsorption (when fats and nutrients are not properly absorbed) that can lead to slower growth and development.
It can also lead to the formation of harmless xanthomas which are fatty deposits under the skin that look like lumps.
Facial features
Children and adults with Alagille syndrome often share physical characteristics, such as a prominent forehead, sunken eyes, and a small chin.
These features do not make children look abnormal, they are just common in those with Alagille syndrome.
Heart or blood vessel (cardiovascular) problems
Besides liver disease, heart problems are one of the most common features of Alagille syndrome.
There may be a narrowing of the pulmonary artery, which is the blood vessel that carries blood from the heart to the lungs (pulmonary artery stenosis).
If it is mild, there may be no symptoms and can only be detected due to a heart murmur that can be heard during a chest exam.
The more severe narrowing of the artery can lead to symptoms such as shortness of breath and fatigue.
There are treatments available that will be discussed with you by your medical team if necessary. The child will be referred to a heart specialist for an evaluation and a treatment plan will be made if necessary.
Eye abnormalities
A ring in the cornea, is an eye condition called posterior embryotoxon, it is a classic sign of the syndrome. The ring is visible during an eye exam.
This occurs when the eye is shaped slightly differently than usual.
This does not affect vision and can only be seen when the eyes are examined with a lamp called a slit lamp.
Many people without Alagille syndrome will have this, but it is more common in people with Alagille syndrome.
skeletal shape
An x-ray can show that the bones of the spine are abnormally shaped.
This can be a single notch or sometimes appears as a “butterfly” shape on the x-ray. This is only visible on an X-ray and does not cause any problems.
Kidney disease
There are also other less common features, such as kidney problems.
The kidneys may be smaller, contain cysts, or simply work less efficiently.
Splenomegaly
Splenomegaly is an enlarged spleen. This can happen due to the increase in blood pressure that occurs in portal hypertension.
If splenomegaly develops, your doctor may recommend that you avoid sports in which a strong direct blow to the abdomen can occur, such as martial arts.
Alagille syndrome diagnosis
The symptoms of Alagille syndrome may resemble other conditions or medical problems.
The doctor will perform an exam and obtain a medical history. Other tests may be done to evaluate if you have Alagille syndrome which may include:
- Liver biopsy.
- Heart and blood vessel tests.
- Eye exams.
- X-ray of the spine.
- Abdominal ultrasound
- Kidney function tests.
- Genetic testing.
A diagnosis of Alagille syndrome is confirmed by a liver biopsy that shows fewer bile ducts than normal and at least 3 of these symptoms:
- Characteristic facial shapes of Alagille syndrome.
- Unusual bone / spine structures such as butterfly vertebrae.
- Unusual heart / blood vessel structures or a heart murmur.
- Liver problems
- A characteristic white ring on the cornea.
Alagille syndrome treatment
Your doctor will determine the best treatment based on the following:
- Age.
- The general health and medical history of the patient.
- The response to specific medications, procedures, or therapies.
There is no cure for Alagille syndrome, but there are treatments that can treat the symptoms of the disease.
The main treatments control liver problems that occur due to the reduction in the number of bile ducts in and around the liver.
Some of the more common ways to manage Alagille syndrome are listed below. They include taking vitamin supplements and medications, evaluating nutrition, and, in rare cases, liver transplantation or other surgery.
Vitamins
When the liver is damaged, some vitamins (A, D, E, and K) may not be properly absorbed from the diet.
Vitamin A is necessary for good eyesight, particularly for seeing in the dark and for the eyes to adapt to changing light conditions.
Vitamin D is necessary for strong, healthy bones and teeth.
Vitamin E is necessary for a healthy nervous system and for the development of coordination.
Vitamin K is necessary to produce clotting factors that help control bleeding.
When the liver is damaged, these vitamins can be given as supplements to ensure healthy levels are maintained. These are usually given by mouth, but sometimes they may need to be given as injections.
Medication
Various medications can be given to increase bile flow and reduce itching. It may be necessary to try a combination of different medications to see what works best for the patient.
Sometimes these medications will only work for a short time.
For more information on administered medications, see the Pruritus page.
Nutrition
A dietitian will evaluate the patient’s diet.
A good flow of bile is needed to break down fat in milk and food.
Babies and children who are jaundiced and do not have a good flow of bile cannot absorb all the fat they eat.
Therefore, children with Alagille syndrome may not gain weight as well as they should.
Babies with Alagille syndrome must often be given special formula milk that contains a type of fat that is more easily absorbed.
Breastfeeding can continue, but the baby may also need a special formula.
Older children may require additional calories that can be given in the form of high-calorie drinks or powders.
The dietitian will advise you on any necessary dietary changes and give you specific advice for the patient.
Alagille syndrome can be associated with poor appetite and eating problems.
For these children the special attention of the dietitian will be necessary.
In some cases, overnight feeding through a nasogastric tube may be recommended.
Liver transplant
Liver transplantation should only be considered for a small group of patients with Alagille syndrome.
It may be necessary if there is severe liver disease causing cirrhosis or if there are symptoms that cannot be controlled in other ways.
Liver transplantation for children with Alagille syndrome can be more complex than other liver transplants because children with Alagille syndrome can also have problems that affect the heart and / or kidneys.
This requires careful research and discussion in each case.
A liver transplant will only be considered when absolutely necessary.
Alagille syndrome complications
Among the complications that may occur, the following have been reported:
- A bleeding in the brain.
- Bone fractures are very common.
- Delay in mental or physical growth and inability for normal development of the individual.
- Diarrhea.
- Heart disease.
- Renal insufficiency.
- Hepatic failure, which occurs in approximately 15% of those affected.
- Malnutrition problems.
- Pancreas disease.
- Eye problems
- Death.
Alagille syndrome prevention
Genetic testing and a discussion of inherited risks within your family can help you make informed decisions about preventing this disease in future generations.
Living with Alagille syndrome
Alagille syndrome can be a serious condition, but many children and adults with Alagille syndrome respond well to treatment and lead normal, happy lives.
The flow of bile often improves as the child grows and develops.
It is difficult to predict which liver disease will get worse over time and which liver will respond to treatment.
