Porphyria Testing

Selecting the appropriate test(s) for porphyria depends on the patient’s symptoms.

Whether urine or plasma porphyrin analysis is ordered depends largely on the patient’s presenting symptoms and the differential diagnosis (see algorithms). In patients presenting with the typical dermatological features of erythropoietic protoporphyria (EPP)/X-linked dominant erythropoietic protoporphyria (XLDPP), plasma (or fecal) porphyrin analysis is indicated because protoporphyrin is not detected in urine. Different groups may recommend either urine or plasma analysis as first-line for screening. At Quest Diagnostics, we currently prefer urine for first-line screening, progressing to plasma or fecal porphyrin analysis if indicated; this may vary depending on your location and performing lab. If urine is difficult to obtain, plasma is a reasonable specimen type.

Typically, a random urine specimen is preferred over a 24-hour collection because porphobilinogen (PBG) and aminolevulinic acid (ALA) may decrease rapidly upon remission in acute intermittent porphyria, hereditary coproporphyria (HCP), and variegate porphyria (VP). Random urine collection also allows for faster results. The 24-hour urine specimen is beneficial in situations where there may be diurnal variations in excretion.  

• Regardless of specimen type, the collection container needs to provide protection from ultraviolet light. If an amber collection jug/urine cup is not available, the easiest way to keep the sample light-protected is to completely wrap the container in aluminum foil so that none of the sample inside is exposed. Please do not use paper towels, disposable gloves, stick-on labels, or other materials to wrap the sample.

• For urine samples, adding sodium carbonate (5 g/100 mL urine) as a preservative is preferred but not required.

Fecal porphyrin analysis is needed to evaluate or confirm the presence or absence of protoporphyrin, which, because of its limited solubility, is not excreted in urine. Protoporphyrin measurement is needed to distinguish between HCP and VP. Elevated protoporphyrin is also seen in EPP/ XLDPP. If the results of urine or plasma testing are suggestive of these disorders, fecal porphyrin analysis is recommended.

• Depending on whether a 24-hour or random urine test has been ordered, patients should keep an amber collection jug or a foil-covered urine cup on hand. Urine should be collected within 24 hours of symptom onset.

• For 24-hour urine collection, all urine should be collected and kept refrigerated during the 24 hour collection period. Once the collection period is complete, the urine specimen should be frozen.

• For a random urine collection, the patient should freeze the specimen immediately after collection.

• The specimen should be brought to a patient service center as soon as possible after collection, for shipment to the testing laboratory. PBG, ALA, and urine fractionated porphyrins should be ordered on the same specimen.

Other conditions that can cause an abnormal porphyrin profile include hematologic disorders, hepatobiliary diseases, drugs, inducers of cytochrome P450 (CYPs), and toxins such as alcohol, lead, and benzene.

False-negative results can be seen if the patient was asymptomatic at the time of sample collection or if specimens were exposed to ultraviolet light.