What's UP Doc?

What's UP Doc? Is a regular column where we feature a patient question along with a response from a member of the UPA Scientific Advisory Board.

Do you have a question you would like to ask a Porphyria Expert?  Send us an email at info@porphyria.org. We’d love to hear from you!

I think I might have Acute Intermittent Porphyria (AIP). My doctor ordered a urine porphyrin test, my porphyrins were high but then I was told that the results aren't considered diagnostic. Why not? And what tests should my doctor order?

Today’s answer comes from Dr. Karl Anderson of University of Texas Medical Branch in Galveston, TX. 

An elevation in urine porphyrins can be seen in many other medical conditions so, by itself, elevated porphyrins are not enough to support a diagnosis of an acute hepatic porphyria (AHP- includes AIP, HCP and VP), and further testing is needed. We recommend testing urine porphobilinogen (PBG) along with urine porphyrins. If both tests are normal at the time of symptoms, AHPs are very unlikely, as are blistering cutaneous porphyrias such as PCT. Protoporphyrias (EPP and XLP) do not elevate urine PBG, they are diagnosed with measurement of red blood cell protoporphyrin.

When AHP is suspected, it is best to order urine porphobilinogen (PBG) and total porphyrins.  A substantial PBG elevation is a strong indication that one of these AHPs is present.  While urine porphyrins aren’t enough on their own to diagnose AHP, we recommend testing for urine porphyrins along with PBG because urine PBG is highest at the start of an attack and can return to normal levels relatively quickly, especially in two rarer types of AHP, variegate porphyria (VP) and hereditary coproporphyria (HCP), whereas urine porphyrins will remain elevated for longer. If both urine PBG and urine porphyrins tests are normal at the time of symptoms, AHPs are very unlikely. If urine PBG or urine porphyrins are elevated at the time of symptoms, additional measurement of porphyrins in plasma and stool is then needed to test for VP and HCP. An isolated increase in urine porphyrins is not an indication of porphyria, and can be seen in many medical conditions.   

If AIP, HCP or VP is found through biochemical testing, genetic testing to identify the underlying mutation is also recommended. 

Genetic testing alone can identify if you have a genetic variant that might cause porphyria, but these variants usually do not cause symptoms, and you will still need biochemical testing to see if you have active porphyria. 

Some important things to know about testing: 

• All biochemical testing for AHP is most sensitive during an acute porphyria attack. If you get a negative result and you were not in an active attack, you may need to be tested again when you have symptoms.
• PBG and porphyrins are light sensitive, so urine samples should either be collected in a dark container or wrapped in foil.  However, brief exposure to light is not harmful. 
• Symptoms and porphyrin elevations in other porphyrias, such as PCT and protoporphyrias, are chronic and testing can be done at any time in most cases. Urine porphyrins is not an appropriate test for some other types of porphyria.

You can contact the United Porphyrias Association at info@porphyria.org or 1-800-868-1292 for support and more information on testing and diagnosis. 

Thank you to Dr. Karl Anderson for this What's UP Doc? answer! Do you have a question for a porphyria expert? Send it to info@porphyria.org.