Acute Intermittent Porphyria (AIP) is probably the most common of the genetic porphyrias. The highest incidence occurs in Lapland, Scandinavia, and the United Kingdom, although it has been reported in other population groups. The incidence of the defective gene in the USA has been estimated at between 5 and 10 in 100,000. The incidence of AIP in psychiatric populations is somewhat higher than in the normal population. The disorder is expressed clinically after puberty and more commonly in women than in men.
Symptoms and Signs
Cardinal symptoms of the porphyrias include photosensitivity, abdominal pain and neurologic disturbances.
Free porphyrins occur only in small amounts in nature. Upon illumination at wavelengths 400 nm, in the presence of oxygen, porphyrins generate singlet oxygen which causes substantial damage to tissues, cells, subcellular elements, and various biomolecules.
Abdominal pain is almost always present and is often the initial symptom of an acute attack. It may be generalized or localized, and in severe cases can be confused with an acute surgical abdomen. Other GI features may include nausea, vomiting, constipation or diarrhea, abdominal distention, and ileus. Urinary retention, incontinence, dysuria, and frequency may be observed. Tachycardia and hypertension, and less frequently fever, sweating, restlessness, and tremor are also observed. In up to 40% of patients, hypertension may become sustained between acute attacks.
Neuropathy is a common feature of AIP. Muscle weakness often begins proximally in the legs but may involve the arms or the distal extremities; involvement may be symmetric, asymmetric, or focal, and may occasionally be associated with a decrease or loss of tendon reflexes. Motor neuropathy may also involve the cranial nerves (most commonly the 7th and 10th) or lead to bulbar paralysis, respiratory deficiency, and death. Sensory patchy neuropathy also occurs when motor neuropathy is severe. Acute attacks of AIP may be accompanied by seizures, especially in patients with hyponatremia due to vomiting, inappropriate fluid therapy, or the syndrome of inappropriate antidiuretic hormone release. The course of an acute attack of AIP is highly variable both in individuals and between patients, with attacks lasting from a few days to several months.
Let's deal with the acute attack first, because this is the most important situation where the diagnosis must be right and must be made fast. If you have acute porphyria, your urine will always contain increased amounts of aminolevulinic acid and porphobilinogen - you will have a positive "watsom-Schwartz" test. If it is suspected that you have abdominal pain or some other symptom due to acute porphyria, this test must be positive. If porphobilinogen cannot be measured in the hospital where you are, either the test must be run immediately somewhere else, or you should be transferred to a different hospital. If the porphobilinogen test is negative, some other cause for the symptoms must be sought. Further, the severity of the acute attack can be followed by observing daily porphobilinogen levels in urine.
When you are not having an attack, AIP is not diagnosed as easily. A 24 hour urine collection can be tested for aminolevulinic acid and porphobilinogen, but if normal levels are obtained, this does not exclude the possibility that you carry the gene for the condition. However, a positive test makes it likely that you do carry the gene for AIP, provided a test of your stool for porphyrins is not adnormal.
A second test can be performed on your blood. This tests for something called "porphobilinogen deaminase" (also called "uroporphyrinogen synthase") and about 90% of patients with the gene for AIP show a reduced level of this. This is called an enzyme test and is only available in a few specialized laboratories. The frequency of false positives and false negatives is rather high and by itself the test is imperfect. However, it is the only test available to test children before puberty.