Porphyrin Tests

Porphyrin testing is used to help diagnose and sometimes to monitor porphyrias. Since the symptoms associated with these disorders may also be seen in a variety of other conditions, testing is also used to help rule out the presence of a porphyria in someone who presents with neurologic/psychiatric or cutaneous symptoms.

For acute attacks, porphobilinogen (PBG) and urine porphyrins may be ordered on a random urine sample. If these are abnormal, they are followed by delta-Aminolevulinic Acid (ALA), PBG, and/or porphyrin testing on a 24-hour urine sample. Fecal porphyrins may be ordered to help distinguish between VP and HCP.

For cutaneous porphyrias, whole blood and urine porphyrins are the most frequently ordered tests. They are used to help diagnose a porphyria and may be used to monitor a porphyria. Enzyme testing, such as PBG deaminase, may be ordered to help detect latent porphyrias in family members of a patient with a diagnosed porphyria.

Tests for PBG and porphyrins may be ordered on a random urine specimen when a patient has symptoms that suggest an acute porphyria, such as abdominal pain, nausea, constipation, peripheral neuropathy (tingling, numbness, or pain in the hands and feet), muscle weakness, urinary retention, confusion, and hallucinations. When the initial tests are abnormal, these tests should be repeated on a 24-hour urine collection to determine how much PBG, ALA, and porphyrins are being excreted. Fecal porphyrin testing may be ordered to help distinguish between porphyrias.

Depending upon the patient’s age and symptoms, a test for urine porphyrins and/or the free erythrocyte protoporphyrin test should be ordered when a patient presents with blisters, scarring, redness, or other skin lesions in sun-exposed areas. A positive urine test is followed by analysis of a 24-hour urine collection to determine which porphyrins are present.

Enzyme testing is most commonly ordered to confirm the diagnosis of acute intermittent porphyria (porphobilinogen deaminase in red blood cells). This test is especially helpful in identifying family members of a known patient who have inherited the disease but have not yet developed signs or symptoms. Some reference laboratories can measure porphyrins in plasma, bile or other fluids, but this is not usually necessary to make a diagnosis.

Care must be taken when interpreting porphyrin test results. Some porphyrins or their precursors may be mildly to moderately elevated in patients with other diseases or conditions. In addition, levels of ALA, PBG and porphyrins may fall to near normal levels between acute attacks of a neurologic porphyria. While negative test results mean that it is unlikely that a patient’s symptoms are caused by a porphyria, positive initial tests should be confirmed with follow-up testing.

ALA and PBG are significantly increased in most patients with an acute porphyria. ALA is less specific than PBG, as it may be elevated in other conditions as well. Specific porphyrins are elevated in each of the porphyrias, and the pattern of elevation (which porphyrin is elevated in which sample) determines the diagnosis. Urine, blood, and stool porphyrins may be increased up to several-fold in a variety of other conditions. Interpretation of the patterns can be difficult. It should be done by a physician or laboratory scientist with expertise in the area.

An abnormal enzyme test or the detection of a gene mutation indicates that a family member has inherited a porphyria. However, enzyme and gene tests cannot determine whether that individual will develop signs and symptoms of porphyria or, if they do, how severe it is likely to be. Fortunately, the majority of gene carriers never have an attack.

Results seen with specific porphyrias include:

A variety of drugs, alcohol, and other environmental factors such as diets, stress, and illness, can trigger acute attacks of a neurologic porphyria in those with latent or inactive disease. By the same token, sun exposure will induce skin lesions in patients with a cutaneous porphyria. Lifestyle modification to avoid aggravating factors is the most effective way to minimize the impact of a porphyria.