What Is Alagille Syndrome?

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Alagille syndrome is a rare liver condition that is passed down through families. It occurs due to the liver's inability to properly remove bile, which is digestive fluid that contains acids, electrolytes, and other substances. This inability is caused by a lack of enough bile ducts to drain bile properly.

Even though Alagille syndrome is primarily considered to be a liver condition, it can also affect other parts of the body, such as the kidneys, heart, eyes, and bones.

This article discusses the symptoms, causes, and treatment options for people with Alagille syndrome. 

Jaundice mono enlarged liver hepatomegaly

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Alagille Syndrome Signs and Symptoms

Since Alagille syndrome can affect various parts of the body, there are many symptoms associated with the disease. The first signs and symptoms often appear shortly after birth and can include:

  • Cholestasis (inadequate bile flow from the liver)
  • Jaundice (yellowing of the skin and whites of the eyes)
  • Inability to gain weight properly
  • Lack of developmental growth following birth
  • Severe skin itchiness (cholestatic pruritus)
  • Heart murmurs (extra sounds in the heart)
  • Congenital heart defects (present since birth)
  • A thicker-than-usual ring around the cornea in the eye
  • Pale-colored stool or dark urine
  • Enlarged liver and spleen
  • Blood vessel stenosis (when certain blood vessels are narrower than they should be)
  • Bluish skin due to a type of heart disease known as cyanotic heart disease (causes low oxygen levels throughout the blood)
  • Possible cognitive or developmental impairment
  • Loss of bone mass
  • Masses of fat that collect underneath the skin

Because the condition can affect various parts of the body, there are various mild, moderate, and severe complications that can occur if someone inherits it.

Complications of Alagille Syndrome

While not everyone will develop complications, there are common health issues associated with the disease. They include:

  • Liver disease and failure
  • Issues with the function of both the kidneys and pancreas
  • Irregular shaped spinal bones
  • Mild vision loss
  • Damage to the retina (part of the eye that transfers visual information to the brain for sight)
  • Electrical disturbances of the heart
  • Malabsorption of nutrients that can lead to another condition known as rickets
  • Tetralogy of Fallot (a type of heart condition that presents with four structural abnormalities)

Causes

Alagille syndrome is hereditary and occurs when there are mutations to two specific genes: NOTCH2 and JAG1. Both genes are tasked with giving instructions to create a certain protein that is used in what's called the Notch signaling pathway. This pathway triggers certain actions within the body that are important for fetal development.

The two genes affected in Alagille syndrome are designed to provide the information to this pathway so that it functions properly. When they mutate, that pathway is compromised. This causes developmental issues.

This type of hereditary condition is considered to be autosomal dominant, which means that only one copy of the gene has to mutate for the condition to develop. The mutated gene needs to come from just one of the two biological parents. There is a 50% chance that someone will develop Alagille syndrome if one of their biological parents has the mutated gene.

In many cases, a child can be born with the gene mutation when neither of their parents has the disease.

Physical Features and Alagille Syndrome

When a person is born with Alagille syndrome, both their health and physical features are affected. Roughly 70%–96% of people with the condition will have distinct facial features, such as deep and wide-set eyes, a pointed chin, a broad forehead that shapes the face like an inverted triangle, and a straight nose with a rounded tip. These facial features are harder to see in infants, but as a person ages, they become more apparent.

Diagnosis

There are various tools used to diagnose Alagille syndrome because of how it affects many areas of the body.

Since liver involvement occurs in up to 100% of people with the disease, one of the first diagnostic steps is examining the liver—specifically, how many bile ducts there are. This is accomplished through a liver biopsy, which involves removing a sample of tissue for examination in a lab. Since as many as 89% of people have inadequate number of bile ducts, this is a necessary step in diagnosing the condition.

Other tests may be used to examine different parts of the body associated with characteristics of the disease. These include:

  • Tests to examine the heart and blood vessels to check for structural abnormalities
  • An eye exam to determine if eye symptoms are present
  • An X-ray of the spinal column
  • Ultrasound of the abdomen
  • Tests that examine how well the kidneys are functioning

A person must have at least three symptoms, along with a lower than normal number of bile ducts, to be diagnosed with Alagille syndrome.

Genetic Testing and Diagnosing Alagille Syndrome

Although genetic testing can be used to determine if a symptomatic person has the gene mutations that cause Alagille syndrome, it is not typically used as a diagnostic tool on its own. In patients with characteristics suggestive of Alagille syndrome, the diagnosis can be made or confirmed by the discovery of a JAG1 or NOTCH2 gene mutation.

Treatment

Treating Alagille syndrome can be a complicated process because the severity of the disease varies significantly from person to person. In more mild cases, the focus may be on nutrition so that malnutrition doesn’t occur due to a lack of vitamin absorption.

If infants or children with Alagille syndrome cannot eat enough, they may have to be given a feeding tube. Supplementing with vitamins may also be an important step in the treatment process, since people with the syndrome are often lacking in various vitamins.

Medications designed to treat certain symptoms may also be used. For example, certain topical or oral medications can address itching of the skin as well as the masses of fat that form underneath the skin.

Other treatment options involve:

  • IBAT (ileal bile acid transporter) inhibitors, which are designed to reduce the levels of bile within the body
  • Medications that improve the flow of bile
  • Repairing the bile ducts to improve flow
  • Liver transplant
  • Partial external biliary diversion surgery, which involves connecting the gallbladder to a stoma (opening or hole) in the abdomen using a piece of the small intestine
  • Heart or kidney surgery to correct any functional or structural issues that have occurred because of Alagille syndrome

Can Alagille Syndrome Be Fatal?

In the most severe cases of Alagille syndrome, life-threatening complications, like liver failure, can occur and lead to loss of life. That said, many people with the disease have a typical life expectancy the same as anyone else.

Prognosis

The prognosis of Alagille syndrome depends greatly on the severity of the disease. Those who experience serious complications, such as fetal heart defects, liver disease, or issues with blood vessels leading to strokes or brain bleeds, have a worse prognosis than those who have only mild symptoms.

While the disease does present some challenges when it comes to quality of life, some people with the disease will have a normal life expectancy. Roughly 75% of people with the disease will live until at least the age of 20.

Coping

Coping with Alagille syndrome depends on how it affects you. For those who are only mildly affected, coping can be simple as long as the medication designed to treat the condition is taken properly.

Coping is much more difficult if the person affected experiences severe complications, it can be that much more difficult to cope. There are, however, resources that you can tap into to make the process more manageable.

The Liver Association of America has a resource center that can help you find online support groups designed to connect you with others who may be going through the same thing.

Summary

Alagille syndrome is a hereditary disease that develops because of problems in how the liver ducts transport bile out of the liver. While the liver is the most notable organ associated with the disease, it can also affect other bodily systems such as the heart, kidneys, eyes, and skeletal system.

Because of the number of body areas affected by Alagille syndrome, the symptoms associated with the condition are varied. Each person with the condition will present differently, and many cases are mild. However, this rare disease can cause serious and even life-threatening complications, so treatment is always necessary.

A Word From Verywell

Watching your child go through Alagille syndrome can be a difficult and heartbreaking process. Fortunately, in many cases, the symptoms associated with the condition are mild in nature, and children can grow up to lead normal lives and have a normal life expectancy.

The best thing you can do is speak to your healthcare provider, follow all instructions for care, and be positive about the outcome of your child’s condition if they do happen to be born with Alagille syndrome.

Frequently Asked Questions

  • What is the life expectancy of someone with Alagille syndrome?

    Most people with the disease have a low life expectancy. Documentation of life expectancy is scarce because of a lack of follow-up in current clinical research, but about 75% of people with Alagille syndrome live until at least the age of 20.

  • Can Alagille syndrome be cured?

    No. There is no cure for Alagille syndrome. However, there are various management techniques that can greatly improve symptoms as well the outcome of the disease. If a person needs a liver transplant because of Alagille syndrome, they will not be cured, but their disease will be much more manageable and their life expectancy improved. 

  • Do adults get Alagille syndrome?

    Alagille syndrome is a genetic condition, so people are born with it. Symptoms usually develop anytime within the first three months of life.

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