What is Porphyria?
Porphyria is the name given a group of very rare metabolic disorders that occur when your body is unable to produce enough of a substance called haem.
Haem is required for many bodily functions. It is a component of haemoglobin, a vital protein which helps transport oxygen around your body and the pigment that gives red blood cells their colour. Haem also helps to form many other important proteins and is found in all body tissues, but mostly in red blood cells, bone marrow and the liver.
To produce haem, your body needs to convert two simple substances, aminol aevulinate acid (ALA)and porphobilinogen (PBG), known as porphyrin precursors, into more complicated substances called porphyrins. These are then converted from one type of porphyrin into another to form, haem.
The steps in this process, or ‘pathway’, are carriedout by seven specialised proteins known as enzymes.If you inherit or develop a defect (usually termed a ‘deficiency’) in these enzymes, the process may not work properly and can cause porphyrins to build up in your body.
This accumulation can either affect the nervous system to provoke ‘acute attacks’ of physical pain or cause damage to your skin – sometimes both.
It can also cause a person’s urine to turn a reddish-purple colour. In fact, the terms ‘porphyrin’ and ‘porphyria’ stem from the Greek word for purple, ‘porphyrus’.
The symptoms you have will depend on which enzyme is affected. There are more than seven types of porphyria, each categorised according to the particular enzyme deficiency and the symptoms associated with it.
Because of this it is difficult to talk about porphyria in general terms. It is possible to divide the disorders into those that mostly affect the brain, known as acute porphyrias, and those that cause skin problems, called cutaneous porphyrias.
‘Cutaneous’ means relating to the skin; disorders that share the characteristics of both are called neurocutaneous porphyrias.
Acute porphyrias are acute intermittent porphyria (AIP), the most common form in the UK and the most severe, and aminolevulinatedehydratase deficiency porphyria (ADP). This form is similar to AIP but extremely rare.
Cutaneous porphyrias are porphyria cutaneatarda (PCT), the most common of the skin disorders and the most common globally; erythropoietic porphyria (EPP), a very uncommon form that causes symptoms very early in life; and the rarest form, congenitalerythropoietic porphyria (CEP), which also occurs early.
Porphyrias causing both acute and cutaneous disorders are hereditary coproporphyria (HCP)and variegate porphyria (VP).
Porphyria can appear in childhood, as seen in erythropoietic porphyria (EPP), but the onset is usually between the ages of 20 and 40 and affects women more than men.
Acute forms can cause serious damage to your liver and kidneys. In some severe cases, people may need a liver transplant. Attacks or seizures can lead to complications such as respiratory failure which can be fatal if not treated. Around 1% of acute attacks of porphyria are fatal.
It is important that the type of porphyria you have is diagnosed as soon as possible. With good management, severe symptoms can be avoided and most people with porphyria (‘porphyriacs’) do in fact lead relatively normal lives.
Acute porphyrias are characterised by attacks of pain and other signs of neurological distress. Incutaneous porphyrias, the build-up of porphyrins and porphyrin precursors interacts with ultraviolet light from sun exposure to cause your skin to become very sensitive to light.
Symptoms do not usually appear until well after puberty and are seen more in women than in men (and more likely to occur during menstruation). The majority of people who inherit the disorder do not have attacks. Where symptoms do occur, they are sudden and can last for days or weeks.
Attacks of acute porphyria may unfold or progress with the following symptoms:
anxiety, restlessness and insomnia
severe abdominal pain
pain in your arms, legs or back
vomiting and constipation
high blood pressure (hypertension)
muscle pain, tingling, numbness, weakness or paralysis
confusion, hallucinations and seizures
breathing difficulties (respiratory paralysis), possibly requiring ventilation
reddish coloured urine.
Acute attacks happen when the levels of porphyrins in your body become very elevated (increased).
They range in severity and usually require having to go to hospital. In the worst case they may require emergency procedures to prevent death.
Whatever the severity of your attacks, it is essential that medical staff act quickly to ensure you receive the appropriate medical treatment.
There is considered to be a slightly increased risk of having an acute attack during or following pregnancy. This risk is reduced if the porphyria you have is already diagnosed and most pregnancies don’t result in problems.
The symptoms of cutaneous porphyrias and neurocutaneous porphyrias usually appear quickly following exposure to the sun. They usually take the following forms:
- itching (pruritus)
- painful skin redness
- skin swelling
- blistering (though not associated with EPP)
- abnormal hair growth on the face can sometimes occur
- reddish coloured urine.
Skin exposed to sunlight is likely to become very fragile, where even slight contact may cause injury to your skin. Areas most at risk are those more commonly exposed, such as your face, neck, hands and feet. In some cases this can lead to permanent skin damage.
A combination of porphyria cutaneous tarda and chronic liver damage may place a person at much higher risk of developing liver cancer, known as hepatocellular carcinoma (HCC).
As porphyria is very uncommon it is often missed or wrongly diagnosed by doctors. Diagnosis is difficult because most symptoms are non-specific, such as abdominal pain, and can often be caused by many other conditions. Even for people with porphyria, it is possible that symptoms can be caused by other underlying problems.
The way in which porphyrins accumulate and the enzyme deficiency that causes this to happen is unique to each porphyria. The doctors treating you cannot make a diagnosis or even distinguish between the various forms based on physical symptoms alone. They will have to carry out appropriate biochemical investigations and correctly interpret the results of these to identify which form of the disease you have.
Tests will examine the following:
- urine test – if you have a form of acute porphyria, a urine test may reveal elevated levels of porphobilinogen and aminolevulinic acids, as well as other porphyrins. It is likely that your urine sample will be sent to a specialised laboratory for this test.
- blood test – if you have a form of cutaneous porphyria, a blood test may show an elevation in the level of porphyrins in the clear, liquid part of your blood (plasma).
- stool sample test – analysis of a stool sample may reveal elevated levels of some porphyrins that may not be detected in urine samples. This test may help doctors to determine the specific type of porphyria affecting you.
Since most types of porphyria are inherited, investigations should also be carried out on children and blood relatives of affected people.
The genes people inherit play an important role in causing porphyria. Genes are responsible for managing the production of proteins that control the cells in your body. In porphyria, the gene that provides the instructions for making the enzymes needed to produce haem has an abnormality, known as a ‘mutation’. This mutation reduces the amount of haem your body can produce.
People inherit two copies of genes, one from each parent. In most types of porphyria, people need to inherit only one copy of a mutated gene, this is called ‘autosomal dominant’ porphyria. In rarer porphyrias, including ADP and CEP, people need to inherit two copies of a mutated gene for the disease.
Genes are only part of the cause of porphyria, however. Most people who carry the genes that can cause porphyria do not actually have the disease. These people are ‘carriers’ or people with ‘latent porphyria’ and could pass the gene onto their children.
There are environmental factors that have an influence on whether people who carry the genes will become ill with porphyria. These can include excess alcohol, excess iron, exposure to oestrogen or other chemicals, viral infections and hepatitis C. The interaction of genetic and environmental factors is not well understood, meaning that for most patients it is not possible to predict or prevent the development of the disease.
As porphyria is an inherited disorder, there is little people can do to avoid acquiring the condition. People whose parents have porphyria may want to take advice on precautions they can take to reduce their risk of developing the condition. Although you may not be able to prevent porphyria, there are a number of treatments and things you can do to manage your condition and prevent attacks.
There is no cure for porphyria. Treatment is aimed at getting rid of or managing your symptoms.
Only drugs known to be safe in porphyria can be prescribed for treatment, as many medications, including common sleeping pills and antibiotics can trigger acute attacks. This underlines the importance of making others aware that you have the condition, and the specific form.
Treatment of acute porphyrias may include:
- stopping medications known or suspected to have triggered your symptoms
- medication to control pain. If pain is severe, opiate-based drugs such as pethidine or morphine are safe to be given. A sedative, chlorpromazine (thorazine) may be used to relax you and help you sleep. Similarly, rapid heart beat and hypertension can be helped with propranolol to slow your heart rate. Anti-epileptic drugs may be given to control convulsion or seizures
- oral and intravenous glucose (sugar) to help you maintain a high energy intake
- haem arginate, a medication that is a form of haem, given to reduce the need for your body to produce its own. Combined with glucose, this lowers porphyrin levels by reducing the formation of aminolaevulinic acid. It is used mainly for severe attacks and is likely to be given to you intravenously over several days. Haem arginate has a rapid effect and an improvement may be expected within one week.
Treatment of cutaneous porphyrias is aimed at reducing the amount of porphyrins in your body to help eliminate your symptoms. This may include:
- phlebotomy, also called venesection, a procedure similar to that used for blood donation in which a quantity of blood (usually up to 500 millilitres) is drawn into a blood donation bag via a needle placed in a vein in your arm. It is carried out to reduce the amount of iron in your body. Phlebotomy is most commonly used for PCT.
blood transfusion, the opposite treatment to phlebotomy. This is used for CEP in order to treat anaemia, in which you lack enough red blood cells.
- a low dose of chloroquine, a drug given in tablet form twice a week.
- beta carotene, given daily for EEP. Made from the orangey-yellow pigment that gives many fruits and vegetable their colour, beta carotene is converted by the body into vitamin A, to promote healthy skin and eyes and to increase your skin’s tolerance to sunlight. It may also colour your own skin a slight orangey shade.
- a bone marrow transplant may be required for people with CEP, where the abnormal gene involved may also affect the formation of bone marrow.
Looking after yourself
Following diagnosis, most people with porphyria are able to lead relatively normal lives by following simple measures to prevent symptoms occurring.
With careful management, some patients are able to experience long periods of time without symptoms or enter remission.
To prevent acute attacks, it is sensible to avoid:
- taking or accepting medication without first checking that it is safe for you. A list of drugs that are considered safe in the treatment of porphyrias can be obtained from the organisations listed below
- illegal psychoactive drugs such as cannabis, ecstasy, cocaine, amphetamines and barbiturates
smoking and drinking alcohol
fasting or following diets that leave you low in energy.
Extra monitoring should be made during pregnancy, when oestrogen levels are elevated.
Wearing some form of medical identification such as a medic alert disc will alert staff to your condition in the event of any emergency treatment.
People with cutaneous porphyrias should stay out of the sun as much as possible. Even exposure to bright light through the windows of a building or car should be avoided. When outside it is advisable to wear sun-protective clothing and heavy sun block containing zinc or titanium.
PCT, the most common skin porphyria, is linked with iron-overload and may cause serious liver damage if not regulated. You may be asked to avoid food rich in iron, vitamin C supplements and high dose oestrogen via contraception.
As is the case in anyone who has a liver condition, alcohol should be avoided.
Diet and exercise
There is no specific diet recommended for porphyria disorders other than eating healthily and making sure meals are taken regularly. This is more important for people who have acute porphyria as they are more sensitive to the effects of certain foods and beverages. This means keeping up a steady intake of calories by eating plenty of carbohydrates.
People who have acute porphyrias commonly suffer fatigue. This may be due to symptoms affecting muscles and joints (such as pain, numbness and weakness) and the sleep disturbance this may cause. In some cases the effects of medication used to control symptoms may contribute to bouts of tiredness.
It is important that your muscles do not get out of condition or reduce in size (atrophy). For this reason it is likely doctors will encourage you to follow a daily exercise routine or to take part in moderate physical activity a few days a week to keep your muscles in shape and to help you sleep better.
You can obtain more detailed advice about diet and exercise from the organisations listed below:
Please visit the support section of our website for information on Support groups in your area or visit our Useful Links section for other organisations who may be able to offer information and support. Other organisations that may be able to offer further information are:
The Drug Database for Acute Porphyria
Download: Porphyria PPH/02/08.pdf
Reviewed by: Dr Adrian Bomford, Reader in Medicine and Honorary Consultant Physician, Institute of Liver Studies, King’s College Hospital, London.