Learn More - Overview of the Porphyrias
The Acute Porphyrias:
Four of the porphyrias cause acute neurological symptoms. They are not common and may be difficult to diagnose. It is estimated that about 1 in 10,000 Europeans or people of European ancestry carries a mutation in one of the genes for acute porphyria, although mutations have been found in all races and many other ethnicities.
Acute Intermittent Porphyria (AIP)
What is Acute Intermittent Porphyria?
AIP is a deficiency of the enzyme hydroxymethylbilane synthase (also known as porphobilinogen deaminase). The enzyme deficiency alone is not sufficient to produce the symptoms of AIP, and other activating factors, such as drugs, hormones, and dietary changes, must be present. Sometimes activating factors cannot be identified. Most people who have a mutation in the gene for AIP never develop symptoms; this is referred to as “latent” AIP. Symptoms may develop after puberty, especially in women.
Acute attacks almost always start with severe pain in the abdomen but sometimes in the chest, back, or thighs, and are often accompanied by nausea, vomiting, and constipation. Heart rate and blood pressure are commonly increased. These symptoms and signs are all due to the effects of the disease on the nervous system. Confusion, convulsions, and muscular weakness, due to impairment of the nerves controlling the muscles, may lead to paralysis. An acute attack usually lasts for days or weeks. Recovery from severe paralysis is generally slow.
Who gets Acute Intermittent Porphyria?
AIP is the most common of the acute porphyrias, with a world-wide prevalence of approximately 1 to 2 per 20,000. AIP is due to a mutation, or change, in, a person’s HMB-synthase (HMBS) gene. It is an autosomal dominant disorder, meaning that a person needs a mutation on only one of his / her HMB-synthase genes to have AIP.
What causes Acute Intermittent Porphyria?
AIP results from a mutation in the gene for the enzyme hydroxymethylbilane-synthase (HMB-synthase), which is also known as porphobilinogen deaminase or uroporphyrinogen I synthase. Other activating factors, such as drugs, hormones, and dietary changes, must be present. Sometimes, activating factors cannot be identified.
Acute attacks are often provoked by drugs such as barbiturates, sulfonamide antibiotics, anti-seizure drugs, rifampin, metoclopramide, and alcohol. Attacks in women may occur after ovulation and during the last part of the menstrual cycle when progesterone levels are high. Reduced food intake, often in an effort to lose weight, as well as infections, surgery, and stressful situations may also precipitate attacks. Risk for developing chronic renal disease and liver cancer (hepatocellular carcinoma) is increased in AIP. The skin is not affected, except in some AIP patients who have developed kidney failure.
How is Acute Intermittent Porphyria diagnosed?
There are many laboratory tests available for the porphyrias, and it is often difficult to decide which should be chosen. Many of these tests are expensive and the results are often difficult to interpret. When abdominal and neurological symptoms suggest an acute porphyria, the best screening tests are urinary aminolevulinic acid (ALA) and porphobilinogen (PBG). DNA testing to identify the specific mutation in an individual’s porphyria-causing gene is the most specific and sensitive test to confirm the diagnosis of a specific porphyria. Before requesting DNA testing, it is recommended that patients have biochemical testing (urinary, stool and/or plasma porphyrins and porphyrin precursors (ALA and PBG) and/or enzyme assays). However, biochemical testing may be inconclusive.
- Also see FAQ: What diagnostic tests are available?
What are treatments for Acute Intermittent Porphyria?
The prognosis is usually good if the disease is recognized and if treatment is prompt, before severe nerve damage develops. Although symptoms usually resolve after an attack, repair of nerve damage and associated muscle weakness may require several months or longer. Mental symptoms may occur during attacks but are not chronic. Premenstrual attacks often resolve quickly with the onset of menses.
Hospitalization is often necessary for acute attacks. Medications for pain, nausea, and vomiting and close observation are generally required. During treatment of an attack, attention should be given to sodium (salt) and water balance. Harmful drugs should be stopped. Attacks are treated with either glucose loading or hemin. These are specific treatments that lower the production of heme pathway intermediates by the liver. Glucose or other carbohydrates are given by mouth if possible, otherwise by vein. However, unless an attack is mild, it is now common practice to begin treatment with hemin, which is more effective than glucose loading. Hemin therapy can be started after a trial of glucose therapy, but the response to hemin therapy is best if started early in an attack.
Patients with severe renal disease tolerate hemodialysis or kidney transplantation. Liver transplantation has been effective for patients with AIP who have repeated attacks and who are resistant to other treatments. However, experience with transplantation as a treatment for AIP is still limited.
What are ways attacks can be prevented?
Attacks can be prevented in many cases by avoiding harmful drugs and adverse dietary practices. Wearing a Medic Alert bracelet is advisable for patients who have had attacks, but is probably not warranted in most latent cases. Very frequent premenstrual attacks can be prevented by a gonadotropin-releasing hormone (GnRH) analogue administered with expert guidance. In selected cases, frequent noncyclic attacks can be prevented by once- or twice-weekly infusions of hemin.
Individuals with AIP who are prone to attacks should eat a normal or high carbohydrate diet and should not greatly restrict their intake of carbohydrate and calories, even for short periods of time. If weight loss is desired, it is advisable to consult a physician and a dietitian to have them prescribe an individualized 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.
