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Types of Porphyria

Acute Intermittent Porphyria

What is Acute Intermittent Porphyria (AIP)?

AIP is just one of the seven different types of porphyria. The enzyme PBG deaminase (PBGD) is defective in people with AIP (Look this up by clicking on the diagram on the right). Thus, such people convert PBG to uroporphyrin with difficulty and may experience a build up of ALA and PBG. The symptoms of AIP relate directly to this.

AIP is an inherited disease. Very rarely, one encounters cases without a history of the disease in the family, but in most, other members of the family will clearly be shown to carry this disease. Not all people with AIP are related however. Research has shown that many different mutations in the gene for PBGD are possible, each having arisen independently at a different place in the world, but all resulting in AIP. Thus, we find AIP in all countries and all races. The disease is particularly common in Scandinavia and parts of northern Europe, but is certainly not confined to people of European extraction.

Inheritance of AIP

AIP is inherited as an autosomal dominant condition. In simple terms, this means that only one parent need be affected for the children to run the risk of showing the disease. In fact, each child will have a 50% chance of inheriting that disease. Both boys and girls stand an equal chance of inheriting the disease.

Will everyone who inherits the gene show the disease?

Not at all. Only some people who have inherited the disease actually show any signs of it. Of the remainder, some will show biochemical abnormalities (an elevated ALA and PBG in the urine) and yet will never have symptoms. Still others do not even show this biochemical disturbance, though direct testing of the enzyme PBGD will prove that they did indeed inherit the disease. Thus, it is true to say that only a minority of patients carrying AIP are ever troubled by the disease. Most will lead happy, fulfilling and relatively healthy and normal lives.

How Do the Symptoms of AIP Come About?

The accumulation of ALA and PBG may be so marked that levels of these substances become very high indeed. This results in a clinical picture known as the acute attack. It is not known whether the ALA and PBG themselves are directly dangerous to the body, or whether it is some other substance which accumulates with them.

Symptoms of the Acute Attack

The acute attack is a specific condition in which an accumulation of ALA and PBG leads to interference with the function of the nervous system. This results in the following symptoms:

  • Abdominal pain which is severe, unrelenting and often felt in the loins and thighs as well as the abdomen.
  • Autonomic instability, leading to vomiting, constipation, hypertension and tachycardia.
  • Possible motor nerve damage, resulting in paralysis. Characteristically, the urine may be very dark which reflects the large amount of PBG and even porphyrins excreted in it during this phase.

Note that this is a very specific complex of symptoms. One cannot ascribe every odd ache, pain or sense of being unwell to one's AIP. After all, there are many people who do not have AIP who experience pain in the abdomen or some nausea from time to time.

Patients with AIP are sometimes told that the disease may be associated with insanity. This is not true. It is known that during a severe acute attack the patient may become anxious, difficult or disturbed. This is only during the period that he is very ill with the acute attack, and he returns to complete normality as the attack passes. There is also no doubt that the vast majority of people with AIP are entirely sane and will remain so.

What Causes the Acute Attack?

  • Porphyrinogenic  medication. This is the commonest factor and is something that must always be guarded against. It is described in more detail below.
  • Fasting.
  • Stressful physical circumstances: such as illness or operations.
  • Attacks associated with menstruation. These obviously relate only to women, and it seems that the women's own hormones (oestrogen and progesterone) may be sufficient to induce acute attacks. This may account for the observation that acute attacks are more common in female than in male patients, even though equal numbers of both sexes carry the disease.

Psychological stress is also felt by some to be a factor, though of course this is very difficult to quantify or prove.

Severity of AIP

We have stressed above that the severity of AIP can vary greatly, from people who have absolutely no sign of the disease to those fortunately rare cases who suffer repeated acute attacks, perhaps associated with the menstrual cycle. Such unfortunate people are in the minority and require specialist assistance. Most people with AIP will do extremely well provided they understand something of their disease, avoid the factors which may trigger the acute attack, and put themselves in touch with physicians who understand something of the disease, or who are prepared to learn more about it. A successful partnership between patient and physician is perhaps the key to a trouble-free life.

How Does AIP Compare to Other Forms of Porphyria?

A major difference between AIP and nearly all the other forms of porphyria is that its only symptom is the acute attack. People with other forms of porphyria often have skin disease; this is never a feature in AIP. The price they pay however is that acute attacks tend to be more easily triggered in AIP than in for instance variegate porphyria (VP) and thus occur more frequently and may be more severe. Similarly, patients with AIP tend to be more sensitive to porphyrinogenic  (dangerous) medication than their counterparts with VP. Thus, people with AIP must take very careful precautions indeed with their medication.

Drug Safety in AIP

Drugs which increase the body's requirement for haem will tend to increase the production of porphyrins. In AIP, this may lead to an aggravation of the problem, a further rise in ALA and PBG, and the acute attack. Basically, drugs may be divided into three classes:

  • Those known to be unsafe in porphyria
  • Those known to be safe in porphyria
  • Those in which the safety is in question, or about which there is no information. Unfortunately this is a very large group.

Read Drug Safety in porphyria for detailed advice on the taking of medication in porphyria. In summary here, let us say the following:

  • Wherever possible, avoid all drugs if you have AIP.
  • If medication is absolutely essential, ensure that you take only those listed as safe in our booklet.
  • Never take a medication whose name does not appear in our list. This is no guarantee that it is safe. It merely means that it has not been tested.
  • If your medical condition is so serious that any other medication or any medication listed as doubtful or dangerous must be taken, then this should only take place under the care of the physician experienced in porphyria.

Who Should Take These Drug Precautions?

All patients known with AIP must follow these precautions. The safest advice is that all their blood relatives, including brothers, sisters and children should take these precautions too, unless they have been adequately tested by a laboratory skilled in the diagnosis of AIP and pronounced clear of this disease. This is because, as mentioned above, some people may not even show increased amounts of ALA and PBG in the urine, and yet may be carrying the disease. An acute attack could arise in them if they take dangerous medication. This also applies to children: it is known that for unknown reasons, children only tend to show signs of porphyria (both by symptoms and by an increased amount of PBG in the urine) after puberty. Yet they are still at risk of an acute attack even during childhood.

How Should the Acute Attack be Handled?

It is essential that anybody with AIP who experiences severe abdominal pain, should immediately cease any medication and report to a doctor. Simple analgesics such as paracetamol and codeine may be used. If these are inadequate to control the pain, then admission to hospital will be necessary. If these are inadequate to control the pain, admission to hospital will be necessary. The pain may then be controlled by morphine and pethidine, but it will be necessary to consider other aspects of treatment including the administration of a specific compound called haem arginate.

Read more about the acute attacks in The acute attack.

Coping With the Frequent and Repeated Attacks of AIP

This is fortunately a very rare problem. It is however potentially unpleasant, not only because of the pain and discomfort of each attack, but because nerve damage may build up and eventually result in some degree of paralysis. Anyone with AIP who has repeated attacks should very definitely be referred to a physician who has experience in dealing with this problem. Special forms of therapy are now available which may help to suppress these attacks. Read more about the management of recurrent acute attacks in Dealing with recurrent attacks of porphyria.

Diagnosis of AIP

It is absolutely essential that all people thought to have AIP and all their family members should be thoroughly and adequately tested so that it is 100% known whether they do have the disease or not. A proper diagnosis is the basis for all further management. Not all laboratories are capable of doing this. At the very least, ALA and PBG must be quantified by chromatographic means. An unambigous elevation is good evidence of AIP. A screening test with Ehrlich's aldehyde's aldehyde alone may be insufficient. In many laboratories, the activity of the enzyme PBG deaminase is measured directly. This is a more accurate method for detecting people who have inherited AIP but show littl or no elevation of PBG.

Specialist laboratories may also be able to examine DNA for an AIP-causing mutation in the gene for PBGD directly. This is the test of choice if the mutation has already been identified in a family member.

Summary

Let us conclude by giving a brief description of patients with AIP who will live comfortably and healthily despite their disease. They have had themselves properly tested by an experienced laboratory such that the diagnosis is beyond question. By studying booklets and notes such as ours and by discussing the problem with their doctor, they understand the disease well. They have also made sure that their family have been properly tested and understand something of the risk of the disease too. They have established a good relationship with a physician who knows something about porphyria or is willing to learn more of it. They have a positive attitude towards the disease and live entirely normally except that they never take unnecessary medication, and always checks drugs they are given against a safety list. In the event of any problems, they know immediately who to turn to and what action to take themselves.