ACUTE PORPHYRIA
1. WHAT IS ACUTE PORPHYRIA?
Acute porphyria is a term that includes three
similar inherited diseases:acute intermittent
porphyria (AIP), variegate porphyria (VP)
and hereditary coproporphyria (HCP). They
are grouped together because acute attacks
of porphyria occur in each one. These attacks
are uncommon and are often difficult to diagnose.
In most European countries, about 1 in 75000
people suffer from them.
Acute intermittent porphyria is the commonest
type. In this disease, only acute attacks
occur and the skin is never affected. If you
have variegate porphyria or hereditary coproporphyria,
your skin may also be affected. In variegate
porphyria, the skin changes and attacks of
acute porphyria may not occur at the same
time.
2. WHAT IS AN ACUTE ATTACK OF PORPHYRIA?
Acute attacks almost always start with severe
pain which is usually in the abdomen but may
also be felt in the back or thighs. Nausea,
vomiting and constipation are common. Some
people may become very confused during an
acute attack and later find it difficult to
remember details of their illness. Convulsions
and muscular weakness, which may lead to paralysis,
are less common symptoms. Pulse rate and blood
pressure may increase but rarely to dangerous
levels. An acute attack usually lasts for
no longer than one or two weeks, but may be
life threatening because of severe neurological
complications like motor paralysis. If paralysis
occurs, recovery is gradual but slow.
Acute attacks are often provoked by drugs,
alcohol, and hormonal changes, for example,
those associated with the menstrual cycle.
Infections and stressful situations may also
precipitate an acute attack. The most common
age for an acute attack is from the late teens
to the forties. They are extremely rare in
children before puberty. Most people have
only one or a few acute attacks;only a minority
suffer repeated attacks, sometimes over several
years. Although acute attacks can be very
severe, particularly if precipitated by drugs
or alcohol, nowadays they are rarely fatal.
Most people who have one or a few attacks
of acute porphyria make a full recovery. They
are then able to lead a normal life except
that they need to take a few simple precautions
to reduce the risk of having another attack.
Women are over 3 times more likely to have
an acute attack due mainly to female hormones (go to chapter 10).
3. HOW IS ACUTE PORPHYRIA INHERITED?
The specific enzyme defect in each type of
acute porphyria is the end result of an alteration
in an hereditary particle of DNA known as
a gene. Therefore a different gene is altered
in each type of acute porphyria. This alteration
is inherited so that each person with porphyria
will often have a number of relatives who
will also have inherited the altered gene.
This means that when two or more people are
affected in the same family they will all
have the same disease. A person newly diagnosed
with porphyria will often have a number of
relatives, both close and distant, who will
also have inherited the altered gene responsible
for the type of acute porphyria in their family.
Many of these relatives may not know that
they have inherited an acute porphyria gene
and that they are therefore at risk of developing
an acute attack and in variegate porphyria
and hereditary coproporphyria, skin disease.
How
is Acute Porphyria Inherited? |
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Dad and 2 children have not got
porphyria |
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Mum
and 2 children have acute porphyria
and are at risk of developing
an acute attack |
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©
Illustrations copyrighted Clare Hollest
This is an example of the inheritance of
an acute porphyria.
In this diagram mum is suffering from porphyria.
She is carrying one normal gene 
and one altered (mutated) gene 
.
Of course, in another family dad could be
suffering from porphyria.
In each case the probability for each child
to inherit porphyria is one in two (50%).
The gene alteration responsible for each
type of acute porphyria is passed down through
families in what is called an autosomal dominant
pattern. Genes, which contain the blueprint
for all the components required by the body,
usually occur in pairs. One of each pair is
inherited from each of our parents. Sometimes
a small error can occur in the copying of
one of these genes resulting in a permanent
gene alteration which is called a mutation.
When a mutation in only one of the pair of
genes causes a disease, as it is the case
in the acute porphyrias, it is called an autosomal
dominant mutation. This altered gene (mutation)
may then be inherited from parent to child
and the risk of an affected person passing
this gene on to any of his or her offspring
is one chance in two (see above diagram).
This risk is the same even if the affected
person has never had any symptoms of porphyria.
Thus the disease often appears to have “skipped
a generation”. Of course, If you have
not inherited the altered gene, you cannot
pass it on to your children.
4. WHAT IS THE RISK OF SYMPTOMS AMONG THOSE
WHO HAVE INHERITED AN ACUTE PORPHYRIA GENE?
Not all people who inherit a gene mutation
for one of the acute porphyrias will develop
an acute attack. It is estimated that at least
three-quarters of people who inherit acute
porphyria will never experience an acute attack
of porphyria. In those who do become ill,
it appears that additional factors are usually
required for an attack to occur. Our knowledge
of these factors is incomplete but among the
most important are a number of drugs, some
of which are widely used, and alcohol. However
acute attacks do occasionally occur in the
absence of any identifiable provoking factor.
Experience over many years has shown that
if people who have inherited one of the acute
porphyrias are careful to avoid certain drugs,
alcohol and other known factors that may provoke
an acute attack, their chance of becoming
ill is much reduced.
5. HOW IS AN ATTACK OF ACUTE PORPHYRIA DIAGNOSED?
For diagnosis of an attack of acute porphyria
and identification of the type of porphyria,
samples of urine, blood and stools (faeces)
need to be carefully tested in a laboratory
that has an expertise in porphyrias (more about porphyria specialist centres). The tests
measure the concentration of porphyrins and
their precursors ALA and PBG which will be
very high in a patient with an attack of acute
porphyria. It is important that these tests
are carried out as soon as possible after
the start of the illness as an accurate diagnosis
may be difficult to establish after recovery
from an acute attack, especially after several
months or years.
In a patient who is known to have inherited
an acute porphyria, it may be difficult to
decide whether an illness is an attack of
acute porphyria or caused by something else.
In this situation, urine and, sometimes, other
tests can often help your doctor to decide
whether you are suffering from an acute attack
or some other illness. It is important that
people with porphyria should not attribute
all their illnesses to porphyria. If they
do, common but potentially serious conditions
like appendicitis may be overlooked.
6. WHEN IS THE BEST TIME TO BE TESTED FOR
AN ACUTE PORPHYRIA?
The best time to be tested for porphyria
is at the earliest opportunity. In practice,
this means that families should be offered
screening for acute porphyria as soon as possible
after a relative has been found to have the
condition. When one or other parent is already
known to have an acute porphyria, their children
should be tested as soon as practicable. It
is worth enquiring about this during pregnancy
as your doctor will then be able to find out
when your baby should be tested. In some cases,
it is now possible to test baby at birth but
it may be necessary to wait until your child
is one year old or, occasionally, even older.
There are two main advantages of early diagnosis.
First, those who are found to have inherited
one of the acute porphyrias can be advised
about how to reduce the risk of an acute attack.
Second, if an acute attack does develop, your
doctor will be able to make the diagnosis
and start special treatment early. The symptoms
of an attack of acute porphyria are not always
easy to recognise and, if the condition is
not already diagnosed, there is a risk that
your doctor will use drugs that may make the
attack worse or may even think that an operation
is necessary.
7. HOW ARE RELATIVES SCREENED FOR ACUTE PORPHYRIA?
For relatives who have not had an acute attack,
and especially for children, urine testing
is usually unhelpful. For these people, special
tests on blood, and sometimes urine or faeces
as well, need to be carried out in a specialist
reference laboratory (more about porphyria specialist centres). For some families, it
is now becoming possible to use DNA tests
to detect the gene mutation that causes porphyria.
DNA tests are more accurate than other methods
but are complicated and are not yet available
for all families. Your doctor should be able
to arrange specialist testing for you. If
you live a long way from a specialist porphyria
laboratory, the samples can easily be sent
by post following specific advice.
8. WHAT CAN I DO TO REDUCE THE RISK OF HAVING
AN ACUTE ATTACK?
Many acute attacks are precipitated by controllable
or avoidable factors such as drugs, alcohol,
fasting (including dieting) or hormones.
Drugs
People with acute intermittent porphyria
must take great care with medication, as many
chemical agents are capable of inducing an
acute attack. It is important ALWAYS
to check the safety of any medicine or remedy
with your doctor (more about drugs). This includes prescription
medicines as well as over-the-counter treatments,
tonics and herbal remedies, some of which
have been known to cause attacks. While over
100 drugs are considered suspect, there are
many other drugs available and good alternatives
can almost always be found.
Some people with porphyria may occasionally
need a drug, perhaps for a serious illness,
that carries some risk of provoking an acute
attack or which has been introduced so recently
that there is little information about its
effect on porphyria. In this situation, your
doctor, after fully discussing and evaluating
the risks, if necessary, in consultation with
a porphyria specialist, may decide to prescribe
the drug for you with special follow-up.
Even though acute attacks are very rare before
puberty, it is safest for children if they
also avoid all drugs that are not known to
be safe in porphyria.
The response of people with porphyria to drugs
that have been reported to produce acute attacks
in others is unpredictable in that a reaction
does not invariably follow in every case.
When there is a reaction, it always takes
the form of an acute attack, which develops
within days of taking the provoking drug. Reactions such as dizziness, feeling faint,
allergies or short-lived skin rashes, which
may occur immediately or very soon after taking
the drug are common after taking drugs and
rarely have anything to do with porphyria.
Alcohol
While many doctors experienced in the care
of those with acute porphyria strongly recommend
absolute avoidance of alcohol, some people
may find this recommendation difficult to
follow. Experience has shown that people who
have experienced an acute attack greatly reduce
the risk of further attacks if they become
teetotal for life. For those shown by testing
to have inherited the gene responsible for
one of the acute porphyrias but who have not
experienced an acute attack, it is best that
they avoid alcohol. However, if this proves
impossible a reasonable compromise is to keep
intake as low as practicable and, in particular,
to avoid heavy red wines, brandy and other
liqueurs.
Diet
Low calorie diets, such as those used to
reduce weight, and prolonged periods with
little food may provoke an acute attack. It
is therefore important to keep to a normal
diet with regular meals, eating enough to
maintain a desirable body weight. People who
have had an acute attack should obtain advice
from a dietician about how this is best achieved
for their particular circumstances. At least
three regular meals should be taken each day;some
people, particularly women with pre-menstrual
problems, may find it easier to eat small
meals every three hours rather than three
normal sized meals.
Patients with severe porphyria, particularly
those who have repeated attacks, may need
special dietary advice from their doctor and
a dietician. If you are overweight, are found
to have an acute porphyria and wish to lose
weight, you should consult your doctor about
the sort of diet that will allow you to lose
weight gradually but safely.
Medical alert card / Warning
jewellery
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It is important to wear
a wrist bracelet, neck pendant and/or
carry a card, that warns that you have
porphyria, at all times. Such warning
is particularly helpful in emergencies
when you may not have an opportunity
to explain that you have porphyria.
Porphyria warning cards may be obtained
by contacting a specialist porphyria
centre in your country (more
about porphyria specialist centres).
Details on warning jewellery can be
obtained from the MedicAlert Foundation,www.medicalert.co.uk.
MedicAlert Foundation International
currently serves members in over 50
countries. |
9. SPECIAL PROBLEMS
Anaesthetics and surgical operations
You must tell your surgeon and anaesthetist
in advance that you have porphyria. A special
anaesthetic that is safe in porphyria will
be needed.
The dentist
You should tell your dentist that you have
an acute porphyria. Dentists often use local
anaesthetic agents and the safety of at least
one of these has been questioned in the past.
Immunisations
All vaccines licensed for human uses are
safe to administer to people who have an acute
porphyria.
10. PARTICULAR ISSUES FOR WOMEN
Women are at least three times more likely
than men to experience an acute attack, due
mostly to female hormones, particularly progesterone.
This hormone is found in the combined oral
contraceptive (the pill), as well as in hormone
replacement therapy (HRT) which is frequently
prescribed for post-menopausal women. Oral
contraceptive and HRT preparations containing
progesterone or related compounds (progestogens)
should be avoided, if at all possible, by
women with an acute porphyria. Injectable
and implantable long-term hormone preparations
are very dangerous and must always be avoided.
In special circumstances, where the risk is
low and the benefits high, your doctor may
consider, after discussion with you and, if
necessary, after consultation with a porphyria
specialist, that the use of progestogen-containing
preparations, particularly in replacement
doses given through the skin from patches,
is justified (more about hormone treatments and oral contraceptives).
Pre-menstrual symptoms
In some women, attacks are clearly related
to the pre-menstrual phase of the menstrual
cycle and your doctor may need to consider
a number of treatment options such as using
special hormones to suppress your periods
for 1-2 years. If you do need this sort of
treatment, it needs to be done under close
supervision by a doctor and will need regular
monitoring.
Pregnancy
Though nearly all pregnancies are uneventful,
there is a small increased risk of having
an acute attack during or after pregnancy.
However, the chances and dangers of such an
acute attack are much diminished if porphyria
has been previously diagnosed. It is therefore
very important for the doctors providing care
during pregnancy to know that you have an
acute porphyria.
11. TREATMENT OF ACUTE ATTACKS
Importance of early recognition and accurate
diagnosis:
Early recognition of an acute attack allows
early treatment. The early symptoms which
herald an acute attack are often easily recognised
by those who have previously experienced an
attack (see chapter 2 "What is an acute attack of porphyria?"). When these symptoms are recognised
you should stop any provoking agents such
as any kind of medication. Immediate intake
of sugary substances such as soft drinks or
glucose tablets may help to reduce the severity
of the symptoms. But you may feel too sick
to do this.
Early recognition is more difficult for those
people who have inherited an acute porphyria
but who have never experienced an acute attack.
As a consequence, there is often considerable
apprehension about pains that usually turn
out to be due to causes other than acute porphyria.
It must be noted that people with porphyria
commonly experience abdominal discomfort,
just like those who do not have the condition,
and a doctor will need to consider other medical
conditions which may cause abdominal pain.
These conditions include a range of bowel
disturbances, urinary infection and sometimes
other urgent medical problems such as appendicitis.
In this situation, the diagnosis of acute
porphyria can usually be established or excluded
by testing the urine for porphobilinogen (PBG).
Treatment of an acute attack:
As soon as an acute attack is suspected,
you should contact your physician for rapid
hospitalisation if the acute episode is severe.
This will allow :
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Biochemical
diagnosis of the acute attack by measuring
PBG in urine. |
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Early
start of specific treatment of the acute
attack : for example, with intravenous
human hemin. |
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Administration
of other medications to treat the various
symptoms accompanying the attack. These
treatments are likely to include the
use of drugs to relieve pain and nausea
and to provide sedation. It is also
important to maintain an adequate intake
of calories and this may require feeding
intravenously or through a naso-gastric
tube. |
Human hemin helps to overcome the relative
deficiency of heme in the liver and takes
away the body’s desire to increase
the supply of the chemicals (porphyrins
and precursors) needed for heme production.
Human hemin is the first choice treatment.
If it cannot be obtained soon enough, large
quantities of glucose, which have a similar
but lesser effect, may be administered in
the meantime.
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