Alagille Syndrome - Children`s Liver Disease Foundation

fighting childhood
liver disease
Alagille Syndrome
a guide
Medical Information Series
Welcome
This leaflet has been written for:
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Parents/carers of a child with Alagille syndrome
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Young people diagnosed with Alagille syndrome
Others who may find this leaflet helpful are:
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Relatives and friends
Healthcare and allied professionals, school, college, university
and nursery teams
This leaflet aims to:
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Explain Alagille syndrome
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Identify the features of Alagille syndrome
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Discuss diagnosis and treatment
Children’s Liver Disease Foundation (CLDF) also has leaflets in its support
series which are available to download from our website –
childliverdisease.org. Leaflets can be mailed to UK patients free of charge,
our contact details are on this leaflet. You may find it helpful to have a copy
of CLDF’s making the most of an appointment leaflet which will help you
prepare for appointments and meetings following discharge.
We also have the following information packs available, free of charge:
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Essential 5 – CLDF’s starter kit of vital information
Education – a pack supporting children and young people under
18 in an educational setting
GP Practice – a pack for families to give to their GP providing a
range of information on childhood liver disease
Friends and Relatives
Yellow Alert – a pack to support CLDF’s Yellow Alert Campaign
for early diagnosis of liver disease in newborn babies
All are available on request to UK families and young adults.
Overseas families should contact CLDF to discuss their literature needs.
What is Alagille syndrome?
Alagille syndrome is the name given to
a particular type of liver condition called
biliary hypoplasia in association with at
least two other signs in other parts of the
body (see below). Alagille syndrome affects
approximately one child in every 100,000
live births and occurs equally between boys
and girls.
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Typical facial features
It is possible to recognise facial features
shared by individuals with Alagille
syndrome. These include a prominent
forehead, deep-set eyes and a small
chin. These features do not make the
child/young person look abnormal; they
are merely clues to the diagnosis.
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Cardiovascular (heart or blood vessel)
abnormalities
There may be a narrowing of the artery
leading from the heart to the lung; this is
called pulmonary artery stenosis. Effects
range from very mild with no symptoms to
being more severe and requiring surgery.
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Eye abnormalities
In particular, posterior embryotoxon
— an accumulation of a substance on
the inner aspects of the cornea. This
can only be seen when the eyes are
examined with a special lamp. It does
not affect vision and is known to be
present in up to 15% of the normal
population, but is more common in
people with Alagille syndrome. Again, its
presence will cause no harm but may
provide a clue to the diagnosis.
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Abnormal shape to some of the bones
in the spine
This may be a simple notch or
sometimes it appears as ‘butterfly-like’
shape on X-ray. This is only visible on
X-ray and does not cause any problems,
but again can give a clue to the
diagnosis.
This syndrome takes its name from
Professor Alagille in France. He was one
of the first people to recognise it in 1975.
It is also sometimes called arterio-hepatic
dysplasia or syndromic biliary hypoplasia.
What are the associated
features of Alagille syndrome
and how do they affect the
child?
It is important to note that both the number
of features and their severity will vary from
one individual to another. As a result,
many people reach adulthood with mild
forms of the condition, are completely well
and are therefore unaware that they have
Alagille syndrome. At the other end of
the spectrum, some babies can be quite
unwell and be diagnosed whilst very young.
Features recognised as being part of the
syndrome include:
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Biliary hypoplasia
The drainage system in the liver is made
up of a tree of bile ducts. These start
very small and join together, like streams
into rivers, to form one large duct that
eventually drains bile into the intestines.
In Alagille syndrome these ducts have
not fully developed and this leads to poor
bile flow causing some degree of liver
dysfunction and sometimes jaundice.
Alagille Syndrome a guide
03
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Other complications have been associated
with Alagille syndrome, but they occur
much less frequently and may include:
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Slower growth
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Kidney problems
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Further abnormalities of the bone
What causes Alagille
syndrome?
The cause of Alagille syndrome is not fully
understood. It is at least partly caused by
genetic changes and this means that other
members of the family may have similar
features to the individual diagnosed with
Alagille syndrome, although they would
probably have much milder symptoms.
Many children/young people with the
syndrome have a mutation (change) in one
particular gene (JAG1). However, this is not
the whole answer as not everyone with a
mutation in this gene has the syndrome. It
is possible that other genes are involved or
factors may play a part. Research continues
into trying to find all the answers.
Genetic Testing
As there is strong evidence suggesting
that there is a genetic element in Alagille
syndrome, it is accepted that there is an
increased chance of subsequent children
having Alagille syndrome once a sibling has
been diagnosed with the condition. Overall,
the risk of a second child being born with
the syndrome is relatively small, probably in
the order of about 1 in 10. In families where
one of the parents has any of the features,
no matter how mild, the chance of having
another child with Alagille syndrome will be
higher.
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Alagille Syndrome a guide
Genetic testing is not currently possible
for Alagille syndrome although it is being
researched and may become possible.
How is Alagille syndrome
diagnosed?
Jaundice, a yellow colouring of the whites
of the eyes and often the skin, is usually
the first sign of Alagille syndrome, mostly
occurring before 6 months of age but
sometimes not noticed up to the age
of 3 years. Diagnosis can be difficult in
the young baby because the condition
may appear very similar to other forms
of liver disease, such as biliary atresia.
To determine the diagnosis, any one or a
combination of the following investigations
may be required:
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Physical examination including looking
at the specific facial features.
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Heart tests
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X-ray — To look for changes in the
bones of the spine.
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Eye examination — To look for changes
associated with the syndrome.
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Blood tests
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Liver biopsy
What is likely to happen?
The abnormality of the bile ducts causes
chronic cholestasis, which means poor bile
flow from the liver into the bowel. This will
affect the general functions of the liver; the
effects can vary considerably from mild to
severe symptoms of the following:
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Jaundice
The degree of jaundice varies from one
individual to another. It can also fluctuate
in an individual.
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Pale Stools
It is bile that gives normal stools their
characteristic colour. Reduced bile flow
therefore results in pale stools.
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Malabsorption
Bile contains substances that help the
food to be broken down and digested.
Poor absorption of nutrients and vitamins
from the gut can occur when bile flow is
poor. This can lead to bone weakness
and rickets.
Pruritus (itch)
Bile salts are usually excreted in the bile.
Poor bile flow leads to a build-up of bile
salts in the body skin which is thought to
contribute to the itching. Itching may be
persistent despite fluctuating jaundice.
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Nose bleeds/Bleeding gums
The liver plays an important role in
producing and storing substances that
control bleeding (e.g. vitamin K). If liver
function is reduced, bleeding may be
more likely.
The following are less common:
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Hepatomegaly
The liver may become enlarged and
develop scar tissue (cirrhosis). The
scarring in the liver can cause resistance
in the blood flow through the liver
resulting in high pressure in the blood
vessels leading to the liver. This is called
portal hypertension.
There is a CLDF leaflet on portal
hypertension which is available on
request.
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Splenomegaly
The spleen may become enlarged
as a result of portal hypertension. If
splenomegaly develops, it is advisable
for him/her to avoid sports where a hard
direct blow to the abdomen could occur.
There is a CLDF leaflet on itch, which is
available on request.
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Xanthelasma/xanthomata
High levels of cholesterol in the blood
(xanthelasma) can result in cholesterol
depositing in the skin (xanthomata).
These look like pale warts and often
appear in the skin creases of children
with severe cholestasis. Xanthomata are
rare before the age of two.
Alagille Syndrome a guide
03
Weetabix, etc. Questran must not be
given within two hours of giving vitamins
as it interferes with their absorption.
How is Alagille syndrome
treated?
There is no cure for Alagille syndrome but
there are treatments that aim to improve
quality of life. The main treatments aim to
reduce the effects of cholestasis.
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Vitamins
As previously mentioned, some vitamins
are often poorly absorbed from the diet.
These are the vitamins usually found in
fats; they are vitamins A, D, E and K.
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Vitamin A is needed for good
eyesight, particularly to see in the
dark and for the eyes to adapt to
changing light conditions.
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Vitamin D is needed for strong healthy
bones and teeth.
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Vitamin E is needed for a healthy
nervous system and the development
of co-ordination.
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Vitamin K is needed to make clotting
factors that control bleeding from
cuts etc.
Extra supplements of these vitamins are
therefore given. Usually these are given
orally but sometimes they may need to
be given by injection.
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Medication
Phenobarbitone, Rifampicin and
Cholestyramine (questran) may be given to
reduce itching and increase the bile flow.
Questran can be given by mixing it well
with liquids but NOT milk to make a drink.
For babies you will be advised to mix it
with smaller quantities of liquid. For older
children the dry powder can be mixed with
foods such as yoghurt, fruit purée,
Alagille Syndrome a guide
Ursodeoxycholic acid is a synthetic bile
salt, which also aims to increase bile flow,
and therefore can help reduce itching.
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Special diet
A dietitian will assess your/your child’s
diet. Good bile flow is needed to break
down the fat in milk and food. Babies
and children who are jaundiced and do
not have good bile flow are not able to
absorb all the fat they eat. Therefore
children with Alagille syndrome may not
gain weight as well as they should and
sometimes even lose weight.
Babies often need to be given a special
formula milk that contains a type of fat
that is more easily absorbed. Breast
feeding can continue but may require a
special formula feed in addition. Older
children may require extra calories that
can be given in the form of high calorie
drinks or powders. Your dietitian will
advise on any necessary dietary
changes and will give specific advice
for you/your child.
Alagille syndrome can be associated with
poor appetite and feeding problems. For
these children special attention from the
dietitian will be necessary. In some cases
overnight feeding via a naso-gastric tube
may be recommended.
A tendency to vomit or regurgitate food
can be associated and may account for
poor growth in some cases.
CLDF has general leaflets on feeding.
These are available on request.
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Liver transplant
Liver transplant only needs to be
considered for a small group of patients
with Alagille syndrome. It may be
considered if there is severe liver disease
causing cirrhosis or there are persistent
symptoms which cannot be controlled in
other ways.
Liver transplantation for children with
Alagille syndrome can be more complex
because of associated problems with
the heart and/or kidneys. This requires
careful investigation and discussion in
each case.
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In General
Alagille syndrome remains a potentially
serious condition. However, it is important
to remember that advances in treatment,
both for the condition itself and the possible
complications, are continuously being
made. The first five years can be difficult.
However, in the majority of cases many of
the symptoms will start to improve between
the ages of 5 and 10 years.
Heart problems
About 90% of children with Alagille
syndrome have associated heart
features. These will be monitored and
treatment given. About half of these
heart problems are of no long-term
significance although some children may
require surgical correction if the child’s
activities are restricted.
Alagille Syndrome a guide
05
Is there a charity taking
action against the effects of
childhood liver disease?
Yes. Started by families in 1980, Children’s
Liver Disease Foundation (CLDF) leads the
way in fighting all childhood liver disease.
CLDF funds vital research, develops
information and awareness programmes
and supports families, young people and
adults diagnosed in childhood who are
living day in, day out with a liver condition
or transplant. And its work has made a big
difference and continues to help save lives.
CLDF has so much to offer you:
information, the opportunity to meet other
families, events and regular updates. To find
out more, call, email or write today:
Children’s Liver Disease Foundation,
36 Great Charles Street, Birmingham,
B3 3JY
0121 212 3839
Main site: childliverdisease.org
Young people’s site: cldf-focus.org
[email protected]
What are the roles of CLDF’s
Family and Young People’s
teams?
CLDF’s Family and Young People’s teams
are here for you, whether you want to talk
about issues affecting you, meet and share
with others or just belong to a group which
cares, knows what it’s like and is fighting to
make a difference. You are not alone.
Our parents say . . .
“. . . We don’t know how we would have
coped without CLDF’s care and support.
They have been just fantastic from the
outset — tremendous people, who are
compassionate and so positive. They really
care about families and children struggling
with liver disease.”
“When Emily was very ill we felt we were on
the sidelines, knowing we couldn’t influence
the outcome and not in control. Getting
involved in fundraising is something you can
control and achieve a positive result. I really
took comfort from that.”
Our young people say . . .
“Knowing CLDF is there is what I need.
I can call whenever I want. Whatever I think
and feel is listened to. Even when I called to
tell them it was my birthday!”
“I feel really well. It’s great that CLDF has
given us the chance to meet other young
people outside of the hospital and have a
fun time. I want them to do more things
like this.”
Families Team
[email protected]
0121 212 6023
Young People’s Team
[email protected]
0121 212 6023
© Children’s Liver Disease Foundation: 2002
Updated: July 2005; April 2006; September 2008; June 2009;
June 2011; March 2012; October 2013; June 2014
Alagille Syndrome a guide
06
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Children’s Liver Disease Foundation is the UK’s leading organisation
dedicated to taking action against the effects of childhood liver disease.
It provides free of charge:
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A huge selection of literature and online animations on the working of the liver available in
print and online
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Information packs for a wide range of audiences, including young people, parents/carers,
GP practices, schools and nurseries, friends and relatives
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Families and young people’s teams providing services in person, online, facebook, text
and phone
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Developing services for adults diagnosed with a liver disease in childhood
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Website – childliverdisease.org
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Young people’s website – cldf-focus.org
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National event programme for families and young people to meet, share and have fun
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Secure online message board – childliverdisease.org/forum
Around 75% of CLDF’s annual income is derived from voluntary donations. Please help us
to continue to support young people, families and adults diagnosed in childhood by making
a donation. You can do this online or by completing the donation form in this leaflet. Even
better, a regular direct debit gift will enable us to plan our work more fully.
Thank you.
Children’s Liver Disease Foundation
36 Great Charles Street
Birmingham
B3 3JY
0121 212 3839
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