Porphyria Types

Acute Intermittent Porphyria (AIP)

Urine can have this appearance during an attack or upon standing in the light.

This is one of the hereditary hepatic porphyrias. Its inheritance is autosomal dominant. The deficient enzyme is porphobilinogen deaminase (PBGD), also known as hydroxymethylbilane synthase. This enzyme was formerly known as uroporphyrinogen I-synthase, and this term is still used by some clinical laboratories. A deficiency of PBGD is not sufficient by itself to produce AIP, and other activating factors must also be present. These include hormones, drugs and dietary changes. Sometimes, activating factors cannot be identified.

Symptoms
Most people who inherit the gene for AIP never develop symptoms. AIP manifests after puberty, especially in women (due to hormonal influences). Symptoms usually occur as attacks that develop over several hours or days. Abdominal pain, which can be severe, is the most common symptom. Others may include:

• nausea

• vomiting

• constipation

• pain in the back, arms and legs

• muscle weakness (due to effects on nerves supplying the muscles)

• urinary retention

• palpitation (due to a rapid heart rate and often accompanied by increased blood pressure)

• confusion, hallucinations and seizures

Sometimes the level of salt (sodium and chloride) in the blood decreases markedly and contributes to some of these symptoms. The skin is not affected.

Diagnosis
Because this disease is rare and can mimic a host of other more common conditions, its presence is often not suspected. On the other hand, the diagnosis of AIP and other types of porphyria is sometimes made incorrectly in patients who do not have porphyria at all, particularly if laboratory tests are improperly done or misinterpreted. The finding of increased levels of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine establishes that one of the acute porphyrias is present. If PBGD is deficient in normal red blood cells then the diagnosis of AIP is established. However, measuring PBGD in red blood cells should not be relied upon by itself to exclude AIP in a sick patient, because the enzyme is not deficient in red blood cells of all AIP patients.

If it is known that someone in a family has AIP and their enzyme value is low in red blood cells, other family Sponsors who have inherited a deficiency of PBGD can be identified by measuring the enzyme in their red blood cells. Latent cases so identified can avoid agents known to cause attacks. However, in some AIP families, PBGD is normal in red blood cells and is deficient only in the liver and other tissues. Falsely low values sometimes occur due to problems with collecting and transporting the sample.

DNA is the material in cells that encodes all the genetic information of an individual. Many different mutations have been identified in the portion of DNA that comprises the gene for PBGD. Almost every family with AIP has a different mutation in this gene. Within one family, however, everyone who inherits a deficiency of PBGD has the same mutation. It is advantageous to know the precise mutation in a family, because that knowledge enables the identification of AIP gene carriers by DNA testing. This approach is much more precise than measuring PBGD enzyme activity in red blood cells. At present, DNA testing for AIP and other porphyrias is available only through a few research laboratories.

Treatment and Prognosis
Hospitalization is often necessary for acute attacks. Medications for pain, nausea and vomiting, and close observation are generally required.

A high intake of glucose or other carbohydrates can help suppress disease activity and can be given by vein or by mouth. Intravenous heme therapy is more potent in suppressing disease activity. It can be started after a trial of glucose therapy. However, the response to heme therapy is best if started early in an attack. Therefore, delaying heme therapy until glucose alone has not been effective may not be warranted unless an attack is mild.

Heme must be administered by vein. Panhematin^®, from Ovation Pharmaceuticals, Inc., is the only commercially available heme therapy for treatment and prevention of acute porphyric attacks in the United States. Heme arginate, which is marketed in some other countries, is another preparation of heme for intravenous administration. It is however, not presently available in the United States. Panhematin^® is less likely to produce phlebitis if it is mixed with human albumin before it is given. (Directions for preparing Panhematin^® in this manner can be obtained from porphyria specialists.) Heme therapy is seldom indicated unless the diagnosis of acute porphyria is proven by a marked increase in urine PBG. How heme therapy should be used to prevent attacks is not well established.

During treatment of an attack, attention should be given to salt and water balance. Harmful drugs should be stopped. These include barbiturates, sulfonamides, and many others. Attacks are often precipitated by low intake of carbohydrates and calories in an attempt to lose weight. Thus dietary counseling is very important (see below). Premenstrual attacks often resolve quickly with the onset of menses; hormone manipulations may prevent such attacks.

AIP is particularly dangerous if the diagnosis has not been made and if harmful drugs are administered. The prognosis is usually good if the disease is recognized and if treatment and preventive measures are begun before severe nerve damage has occurred. Although symptoms usually resolve after an attack, some patients develop chronic pain. Nerve damage and associated muscle weakness can improve over a period of months or longer after a severe attack. Mental symptoms may occur during attacks, but are usually not chronic.

Wearing a Medic Alert bracelet is advisable for patients who have had attacks but is probably not warranted in most latent cases. It should be remembered that AIP patients can develop other diseases, and symptoms may not always be due to porphyria.

Diet
AIP patients prone to attacks should eat a normal or high carbohydrate diet and should not greatly restrict their intakes of carbohydrate and calories, even for short periods of time. If weight loss is desired, it is advisable to consult a physician who may then request that a dietitian estimate an individual's normal caloric intake, which varies greatly from one person to another. Then it may be appropriate to prescribe a diet that is approximately 10% below the normal level of calories for the patient. This should result in a gradual weight loss and usually will not cause an attack of porphyria.

Having Children
Pregnancy is tolerated much better than was formerly believed. Offspring have a 50% chance of inheriting the gene for AIP, but the great majority of them remain "latent" for all or most of their lifetimes. The minority that eventually have symptoms usually benefit from treatment. Given these considerations, most patients or individuals with "latent" porphyria elect to have children for the same reasons as anyone else.

For more information please see AIP, HCP, VP, & ADP.