Alagille Syndrome

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Key points

Alagille Syndrome is a genetic disorder that babies are born with
People with Alagille Syndrome have fewer bile ducts than normal, so bile can’t flow properly
It causes liver problems and can affect the skin, heart, bones, spine and kidneys. These problems can be quite mild or serious and even life-threatening
Alagille Syndrome can be diagnosed at any age
Children with Alagille Syndrome may need a special diet and close medical monitoring to prevent complications
Some people with Alagille Syndrome go on to need a liver transplant.

Transcript

Jasper: I probably first found out the severity of it maybe when I was five, five or six, about when I first found out like I could not be here.

Peter: Yeah it was probably more when he first started school, like, because we had to do obviously all the paperwork you’ve got to list medications and conditions and things like that.

Jasper: Well, my name’s Jasper, I have Alagille Syndrome. I do like drawing, I do little drawings of like military planes. After seeing Top Gun when I was little. I think after I saw the movie, I was like I want to be a pilot. I would like to be studying for my pilot’s licence. I love watching little documentaries on how they built the planes, how you become a pilot. Yeah, I want to give it a go.

Peter: He was a bit yellow at the time and we just came down here for a visit to see grandparents. We thought, oh it’s only three months, it’ll, jaundice usually goes away. We were told it would probably go away as well, but we took him for a, like, just a ride in the stroller and we went over a bit of bumpy road and he got a bruise on his arm and his arm started to swell.

The day of the diagnosis, it was quiet, we went in, saw the doctor, he sat us both down and he said your child has this, it’s classed as chronic organ failure. And obviously just felt wiped out inside. So it definitely brought his mum to tears and I was sort of sitting in stunned silence. As soon as you hear that news you’re on the floor. Obviously, you don’t know what to do next and what’s going to happen, but the doctors, the good support team, they just said yeah well this is what we got to do, this is what we can do to manage it.

I got posted down here to Puckapunyal and then after my time there I was going to be posted to either back to Darwin or Adelaide, but we thought, well, Jasper’s specialist in the hospital’s here and he’s got two younger brothers ,so we thought oh I’ll get out of the army and we’ll stay down here.

Alagilles being, well, what it is, so his liver’s not getting rid of bile acids, so which also means it comes out through his skin so a lot of scratching.

Jasper: Yeah, I remember I had one really bad night, I could not stop scratching, there was blood blisters all over my legs and arms, lots of hospital visits.

Peter: Lots and lots of blood tests.

Jasper: Well, lots of medicines.

Peter: Yes because as he grows, obviously his medications change and dosages and things like that.

Jasper: I’d get told like we’re going to up the dosage because like something might be too low or too high. It’s constantly just trying to get everything right so I’m like not too high or not too low, or else I could get very sick.

Peter: Like mixing a cake.

Choosing schools was a big thing, teachers were all good they all loved him and took care of him. Then we also had a handy little booklet that says I’ve got this that they could hand out to the kids, but it was all written for kids as well. Sport was another thing. He can’t really do contact sport because his liver and spleen’s enlarged, so a decent hit like playing football or anything like that could get a bit interesting. So cricket’s been his chosen sport now.

Jasper: When I like knew dad was in the army I wanted to be in the army as an infantry man, but I found out I couldn’t do that because of my condition, so then I had to find something else to do and I saw I found cricket.

Peter: Possible outcome will be liver transplant. There’s always a thought, yeah, we might have to have the surgery, what are we going to do then?

Jasper: Yeah the liver transplant is a bit scary knowing that it is a very close thing that could happen. But I’d rather do it after schooling, so I’m not stuck at home trying to catch up.

One of my mates he’s well aware what could happen, yeah. We can both bounce things off each other, like what’s going on in his life, what’s going on in mine but, yeah, it’s good friendship support.

Everyone’s journey is different like mine can be completely different to someone else like they might have something else from me. But what I would say is just don’t worry about it that much.

Interviewer: How do you feel about that dad?

Peter: Oh I’d agree, I’d agree, I’d say don’t listen to Google either.

Jasper: Well, when I was first diagnosed, like, I was itching pretty bad but now since I’m on my medicine, way better.

Peter: Yeah, now look at him.

Jasper: I always take the doctor’s advice seriously, like, listening to my doctors, listening to my parents.

Peter: That’s a new one.

Jasper: I listened when I was younger.

Peter: Yeah, okay, I agree with that, he was better when he was little. Teenagers are stubborn.

Transcript

Alagille Syndrome is a rare genetic condition which affects multiple parts of the body. The gene that has the defect in it is usually something called JAG1, and in some patients there’s another gene involved called NOTCH. These genes are very important in regulating development of the body very early in life, and therefore lots of different systems and parts of the body are affected.

The JAG and NOTCH gene mutations that cause Alagille Syndrome are inherited usually from a parent, one or other parent, in about half the children with Alagille Syndrome. In the other half, the mutation occurs spontaneously in the child. In the children where the parent, one or other parent, is affected, because Alagilles is so variable, the parent may be so mildly affected that they may not even know they have the disease. They may have no symptoms or signs or any abnormal blood tests, and it’s only when the child develops symptoms that we know that the parent, by testing them, has Alagille Syndrome.

Alagille Syndrome predominantly affects the liver, but also the heart, the blood vessels in the brain, the kidneys and the eyes. The symptoms of Alagilles depend on which part of the body is predominantly affected, and often more than one part of the body is affected.

So if you have liver disease, you can present as a baby with jaundice early in life, that’s yellow colouring of the eyes and the skin, and you can develop progressive liver disease with failing to gain weight, diarrhoea and very, very severe itch. You can also develop xanthoma, which are little lumps of cholesterol under the skin.

Another major system that’s affected is the heart, and often there is narrowing or abnormality of the blood vessels in the heart and the lungs, and this can present with the baby looking blue at birth and needing some urgent treatment.

The other features of Alagilles are a little bit more subtle and need tests to find them. So for instance, the changes in the bones and the changes in the blood vessels in the brain require special scans in order to be able to detect them.

The treatment for Alagille Syndrome depends on, again, which system is affected. So if it’s the liver disease, we initially provide special formulas and supplemental vitamins so that the child can grow properly. If there is a very severe itch, we have a range of medications. In fact, this is one of the areas of medicine that’s advanced quite a lot. We’ve got some very interesting new medications which will shortly be licensed for use that treat the very, very severe itch in Alagille Syndrome. If the liver disease progresses, then perhaps a liver transplantation may be required, but it’s not required in everyone.

The heart disease needs treatment based on how severe it is, and often children will see a cardiologist and have special scans done to determine whether they need any surgery or just monitoring.

Life with Alagille Syndrome, again, is very variable because it is such a variable condition. Some people are very, very mildly affected and don’t even know they’ve got Alagille Syndrome until they’re adults and may have some abnormal kidney tests or have an x-ray which shows some abnormality in the vertebrae. Other babies present very, very early and are extremely sick and have a liver transplantation within a year of life because they are very sick.

So the life with Alagille Syndrome is very variable according to how badly you are affected. We have had children who have been very severely ill at birth, who have grown up, required liver transplantation, got married and had children. So there is a good outlook as well.

I think it’s important that the diagnosis is made early, so if there are any suspicious symptoms or if your doctor feels that there are features of Alagille Syndrome, it’s important to get referred early to a specialist hospital, in fact, and with a paediatric gastroenterologist who can look after the many aspects of Alagille Syndrome together with other specialists in the heart and eyes and kidneys, etc. It’s important to maintain a healthy diet and, of course, a positive outlook on life.

We don’t really understand why two people with the same gene mutation can be so different. For instance, in the case of the parent who is completely well with no symptoms and the child who has the same mutation, who has very severe liver disease from birth. There are a lot of scientists working on that question because it is a very tricky one.

Having Alagille Syndrome can be very confusing and very complex. So if you need to reach out for additional help, there is plenty of help available. I would suggest the Liver Foundation website that has lots of information and also where to get other information from.

In addition, I would definitely suggest that you reach out to your doctor because they will understand most about what types of Alagilles symptoms affect you the most and therefore what you need to be looking out for.

And then finally, I’d like to mention the GALA study, G-A-L-A. That’s the Global Alagilles Alliance of which we are a part. That is a multi-centre international study looking at Alagilles patients from all around the world.

Because it’s a rare disease, we learn a lot more when we pull all of the information together. This GALA consortium has published a lot of papers which are available on the internet for families to read.

What is Alagille Syndrome?

Alagille Syndrome is condition that affects the liver and many other parts of the body. It’s very rare. Only about 1 in 30,000 to 45,000 people have this condition.

Babies born with Alagille Syndrome don’t have enough bile ducts to drain bile from the liver. Bile builds up in the liver and causes liver damage. Liver problems are usually the first sign of Alagille Syndrome and often develop in the first 3 months of a baby’s life. The baby may develop jaundice (yellow skin and eyes) due to a build up of bilirubin in the blood.

Diagram of the liver showing bile ducts and pancreas

Alagille Syndrome can also affect other parts of the body. Someone with Alagille Syndrome might have:

Enlarged spleen – because the liver isn’t working well so blood builds up in the spleen
A heart murmur – because the blood vessels that take blood from the heart to the lungs are too narrow
Abnormal blood vessels in the head or neck
Kidney disease, because the kidneys are smaller than usual or they have cysts
Changes in the bones of the spine.

Alagille Syndrome can be so mild in some people that they don’t know they have it. In others it can be much more serious and even life-threatening. Complications of Alagille Syndrome may include:

Heart problems
Kidney failure
Pancreas problems
Bleeding into the brain or a stroke.

The liver problems stop the body from absorbing vitamins properly. This can cause other issues such as:

Bone fractures or rickets
Poor weight gain, delayed mental or physical growth, failure to thrive
Vision problems
Blood clotting problems.

Six of every 10 children diagnosed with Alagille Syndrome will develop liver failure by the age of 18. But in some babies, the jaundice clears up (levels of bilirubin in the blood drop). If the bilirubin in the blood is less than 5mg/dL between 6 and 12 months of age, then the baby will have an 8 in 10 chance of reaching adulthood without needing a liver transplant.

People with mild Alagille Syndrome often lead normal lives and only become aware they have Alagille’s Syndrome when another family member with more serious medical problems is diagnosed. We don’t know why members of the same family can be so differently affected by Alagille’s Syndrome.

What are the symptoms of Alagille Syndrome?

Symptoms usually start before a baby turns 1. Alagille Syndrome can cause blocked flow of bile from the liver (called cholestasis) followed by liver damage.

Symptoms of Alagille Syndrome in babies and children include:

Yellow skin and whites of the eyes (jaundice). This is often the first sign. Many babies have jaundice, but if the baby has Alagille Syndrome it won’t go away
Pale poo and/or dark urine
Enlarged liver
Very itchy skin (called pruritus).

Later, children with Alagille Syndrome may have stunted growth and development.

Other signs a baby or child might have Alagille Syndrome are:

Hard bumps just under the surface of the skin (called xanthomas)
A certain appearance (in slightly older children) – deep-set eyes, a wide forehead, straight nose and small chin
A white ring in the eye (called a posterior embryotoxon) that can be seen in a special eye exam)
Bone or spine abnormalities
Unusual heart/blood vessels and/or a heart murmur.

How is Alagille Syndrome diagnosed?

It can be quite difficult to diagnose Alagille Syndrome because the symptoms can often mean something else.

If you are worried your child has Alagille Syndrome, talk to your doctor. They will examine your child and may send them off for other tests including:

Ultrasound of the belly to check the liver, spleen and kidneys
Blood tests to check the liver and kidneys and look at the nutrients in the blood
A liver biopsy (where a small sample of liver is removed to study in the laboratory) to see whether there are too few bile ducts
X-rays of the spine
Eye tests
Testing of the heart and blood vessels ( chest Xray, echocardiogram)
Blood test to confirm the abnormal gene

Why did I get Alagille Syndrome?

Alagille Syndrome happens because a baby is born with a faulty gene. Most cases are caused by changes to the JAG1 gene. A few cases are caused by changes to the NOTCH2 gene.

Sometimes these genes are inherited from one parent. If one parent has Alagille Syndrome, their child has a 50:50 chance of being born with it.

But in about half of Alagille Syndrome cases, neither parent has the condition. It just happens.

If someone is diagnosed with Alagille Syndrome, the whole family might be offered genetic testing. This will show whether anyone else in the family has the affected genes. It can show whether other family members might need treatment, and can help parents plan future pregnancies.

How is Alagille Syndrome treated?

There is no cure for Alagille Syndrome. Someone with Alagille Syndrome will probably see a team of specialists to treat problems with their liver, heart, kidneys, bones and eyes.

There are different treatments depending on what problems the person has.

To improve the flow of bile from the liver: Medicine or surgery.
To keep the child growing and developing properly: Special food or vitamin supplements (either by mouth or injection).
To stop the itching: Several new medicines have recently become available to relieve itching.

If Alagille Syndrome causes liver failure, your child will need a liver transplant.

Treatments may need to change over time, so it’s important to stay in touch with the medical team.

Living with Alagille Syndrome

Someone with Alagille Syndrome may need a high-calorie diet and extra calcium and vitamins A, D, E, and K. Some children with Alagille Syndrome may need to be fed via a tube passed through the nose to the stomach.

Usually, children with Alagille Syndrome can do normal physical activity, but if they have an enlarged spleen, they may be asked to avoid contact sports.