Porphyria Causes, Symptoms, Diagnosis, Treatment, Prevention

Porphyria Causes, Symptoms, Diagnosis, Treatment, Prevention


What is porphyria?


Porphyria is a term that refers to a group of disorders - the porphyrias - that affect the nervous system or skin, or both. Each type of porphyria is due to the deficiency of one of the enzymes needed to make a substance in the body called heme. Enzymes are proteins that help chemical reactions happen in the body. Making heme involves a series of eight different enzymes, each acting in turn.

Heme is a red pigment composed of iron linked to a chemical called protoporphyrin. Heme has important functions in the body. The largest amounts of heme are in the blood and bone marrow in the form of hemoglobin within red blood cells. Hemoglobin gives blood its red color and carries oxygen from the lungs to all parts of the body. In the liver, heme is a component of proteins that have many functions, including breaking down hormones, drugs, and other chemicals and generating high-energy compounds that keep liver cells alive and functioning normally.

The body makes heme mainly in the bone marrow and the liver. The process of making heme is called the heme biosynthetic pathway. Each step of the process is controlled by one of eight enzymes. If any one of the enzymes is deficient, the process is disrupted. As a result, porphyrin or its precursors - chemicals formed at earlier steps of the process - may build up in body tissues and cause illness.

The different types of porphyria


The porphyrias are a group of diseases and each is named in the diagram above, depending on which enzyme is lacking. However, the porphyrias are also commonly classified according to the effects that they have on the body and the symptoms that they produce. Porphyrias can be:

Acute porphyrias


Symptoms of acute porphyria can vary. The most common symptom is a severe abdominal (tummy) pain. The nervous system is also commonly affected to cause symptoms such as muscle weakness and numbness in parts of the body. Acute porphyria can also cause mental health (psychiatric) problems including agitation, mania, depression and hallucinations. Symptoms are described more fully later. If there are both nervous system and psychiatric problems these are sometimes put together and called neuropsychiatric problems. The acute porphyrias include:

  • Acute intermittent porphyria.
  • Aminolaevulinic acid dehydratase porphyria (also known as plumboporphyria).

Cutaneous porphyrias

This type of porphyria mainly affects the skin. The cutaneous porphyrias include:

  • Porphyria cutanea tarda.
  • Erythropoietic protoporphyria.
  • Congenital erythropoietic porphyria (also known as Günther's disease).

Mixed porphyrias


This type of porphyria can lead to symptoms of both acute porphyria and cutaneous porphyria. They can therefore cause abdominal pain, affect the skin and the nervous system, and may also cause psychiatric problems. The mixed porphyrias include:

  • Variegate porphyria.
  • Hereditary coproporphyria.

Causes of Porphyria


Each type of porphyria has the same root cause - a problem in the production of heme. Heme is a component of hemoglobin. That's a protein in red blood cells that carries oxygen from the lungs to the rest of the body.

Heme contains iron and gives blood its red color. The production of heme takes place in the liver and bone marrow and involves eight different enzymes. A shortage of any of those enzymes can create an excess buildup of certain chemical compounds involved in producing heme. The specific type of porphyria is determined by which enzyme is lacking.

Most types of porphyria are inherited. About half of them occur when one altered gene is passed from just one parent. The risk of developing a porphyria or passing it to your children depends on the specific type.

Porphyria cutanea tarda, on the other hand, is often an acquired disease. Although the enzyme deficiency that causes PCT can be inherited, most people who inherit it never develop symptoms. Instead, the disease becomes active when the deficiency is triggered by certain conditions or lifestyle choices. These include:


Porphyria can be triggered by other:

  • Drugs such as barbiturates, tranquilizers, birth control pills, and sedatives
  • Chemicals
  • Fasting
  • Drinking alcohol, especially heavy drinking
  • Infections
  • Emotional and physical stress
  • Menstrual hormones
  • Exposure to the sun

What are the symptoms of porphyria?


Symptoms of Acute Porphyria


The symptoms of acute porphyria can develop quickly and last for days or weeks. A salt imbalance sometimes accompanies an episode of this type of porphyria. The imbalance can contribute to some of these symptoms:

  • Chest pain
  • Abdominal pain, often severe
  • Increased heart rate and blood pressure
  • Limb and back pain
  • Muscle weakness
  • Tingling
  • Loss of sensation
  • Cramping
  • Vomiting and constipation
  • Personality changes or mental disorders
  • Agitation, confusion, and seizures

Long-term complications in some patients have included:


Symptoms of Cutaneous Porphyria


Symptoms of cutaneous porphyria occur when the skin is exposed to sunlight. The most commonly affected areas include the back of the:

  • Hands
  • Forearms
  • Face
  • Ears
  • Neck
The symptoms include:

  • Blisters
  • Itching
  • Swelling of the skin
  • Pain
  • Increased hair growth
  • Darkening and thickening of the skin


How is porphyria diagnosed?


Doctors diagnose porphyria using blood, urine, and stool tests. Interpreting test results can be complex, and initial tests may be followed by further testing to confirm the diagnosis. Diagnosis may be delayed because the symptoms of porphyria are similar to symptoms of other disorders.

Treatment of Porphyria


Outbreaks of symptoms of acute porphyria often require hospitalization. Patients may be given medicine for pain, nausea, and vomiting. They will also often receive glucose or Panhematin (hemin) injections. Panhematin is the only heme therapy approved for use in the U.S.

Severe attacks of acute porphyria can cause lasting nerve damage and muscle weakness that can take months to resolve.

Treatment of cutaneous porphyria depends on the specific type and the severity of the symptoms.

Treatment of porphyria cutanea tarda includes:

  • Regular blood removal (phlebotomies) to reduce the amount of iron in the liver
  • Low doses of the antimalarial drug chloroquine or hydroxychloroquine
  • Avoidance of triggers


Acute porphyrias


Acute porphyrias


The most common of these is acute intermittent porphyria. However, the mixed porphyrias (hereditary coproporphyria and variegate porphyria) can also show the same symptoms. Aminolaevulinic acid dehydratase porphyria (also known as plumboporphyria) is very rare.

With this type of porphyria, symptoms tend to come in waves (or as an attack). Between attacks the person is healthy. The frequency and severity of attacks also vary widely between people. It is estimated that at least three quarters of people who inherit an acute porphyria gene will never experience an acute attack of porphyria.

An attack may be precipitated (brought on by) a number of things, including certain drugs, smoking, alcohol, illicit drug use, emotional upset, pregnancy, menstruation, injury, a surgical procedure and sometimes infection somewhere in the body.

There are certain drugs that you should avoid if you have this type of porphyria. Recommended lists of drugs to avoid are available. Remember that herbal remedies and over-the-counter drugs may also be included in the list of recommended drugs to avoid. Always ask your doctor or pharmacist.

What happens during an acute Porphyria attack?


The most common age for a first acute attack is anywhere from your late teens to your forties. An attack can go on for one to two weeks. Attacks can often start with anxiety, restlessness and insomnia (difficulty with sleeping). You may also develop abdominal pain which can be severe. Nausea, vomiting and constipation can occur. Nervous system effects can lead to speeding up of your heart rate, and an increase in your blood pressure. You may notice that your urine is dark or reddish because your kidneys are trying to get rid of the excessive haem precursors.

Some people can develop muscle weakness during an acute attack. This can affect your arms and legs and sometimes even your chest wall muscles, leading to breathing difficulty. Your sensation may be affected. Rarely, confusion and convulsions can occur.

You may experience mood changes including agitation and/or euphoria and sometimes depression or hallucinations. In some people, these psychiatric problems can persist between attacks.

Rarely, sudden death can occur during an acute attack. This is thought to be due to a disturbance in the electrical activity in your heart (cardiac arrhythmia).

Cutaneous porphyrias


This type of porphyria mainly affects the skin, causing skin rashes and other problems. The excess porphyrins that build up can interact with light, making the skin light-sensitive. There are various different types which can produce slightly different symptoms.

Porphyria cutanea tarda


Symptoms due to this type of porphyria are usually first noticed in your 40s. When your skin is exposed to sunlight, redness and blisters can appear. Your skin can become quite fragile and can take a long time to heal. Your skin may be itchy and there may be areas where it is hyperpigmented (darker) or excessively hairy. The skin on the forehead, cheeks, ears and backs of the hands is most commonly affected but all skin exposed to the sun can be affected. Some people with porphyria cutanea tarda can develop liver damage.

Because the skin problems can be triggered by sunlight, one of the main treatments is to avoid exposure to sunlight by covering up and using sunscreens. Avoidance of alcohol and drugs, such as the contraceptive pill, may also be helpful. A drug called chloroquine may also help to treat this type of porphyria in some people. This medication makes the excess porphyrins more soluble so that more are excreted (passed out) in the urine. 

In some people with porphyria cutanea tarda, there can be a build-up of iron in the body. If this is the case, excess iron can be removed by regularly removing blood using a procedure called venesection. The procedure is the same as for blood donors. Every pint of blood removed contains a quarter of a gram of iron. The body then uses some of the excess stored iron to make new red blood cells.

Congenital erythropoietic porphyria


This is a very rare form of porphyria. It is also sometimes known as Günther's disease. Symptoms are usually first noticed in childhood. You may notice that your child's urine appears red in their nappies. Their skin is also extremely sensitive to sunlight. The skin can become red and develop blisters. These blisters can burst and ulcers can form which may become easily infected. When the skin ulcers heal, there may be scarring of the skin, which is sometimes severe. 

Children with this type of porphyria can become anaemic and their spleen can enlarge in size. Possible treatments include a drug called chloroquine, splenectomy (removal of the spleen) and sometimes a bone marrow transplant.

Erythropoietic protoporphyria


Again, symptoms are usually first noticed in childhood but they can occur for the first time at any age. There is burning, itching and redness of the skin on exposure to sunlight. In this form of porphyria, blisters do not tend to form and there is minimal scarring of the skin. Porphyrins and other precursors can build up in the liver and lead to liver failure. Gallstones can also occur. 

It is diagnosed by measuring haem precursor levels in red blood cells. Treatment with carotene may be helpful, as it raises tolerance to sunlight. Liver and bone marrow transplantation have also been successfully carried out as other treatments.

Mixed porphyrias


Skin symptoms occur in about half of people with variegate porphyria and about a third of people with hereditary coproporphyria. The skin rash is similar to that in porphyria cutanea tarda (see above). Sometimes the only symptom of these mixed porphyrias is the skin rash. However, it is important to find out the exact type of porphyria, as those with mixed porphyrias are at risk of developing neuropsychiatric acute attacks as well.

How to Prevent Porphyria


Genetic testing may identify people at risk for porphyria. If there are people in your family with the diagnosis of porphyria, you may be eligible for testing. If the family member has had a test that showed DNA changes, that change can be looked for in you.

A genetic counselor can review your family history. The counselor will help find the risks for this disorder in you and your offspring. They will also discuss appropriate testing for you.

Genetic mutation cannot be corrected. However, attacks can be anticipated, prevented, or controlled. Steps to avoid porphyria attacks and complications include the following:
  • Protect skin from injury or infection
  • Avoid drugs and other triggers
  • Don't use alcohol or illegal drugs.
  • Avoid fasting and dieting that involves severe calorie restriction.
  • Don't smoke.
  • Minimize sun exposure.
  • When you're outdoors, wear protective clothing and use sunscreen.
  • Treat infections and other illnesses promptly.
  • Reduce stress.