PRACTICAL STEPS IN DIAGNOSING PORPHYRIA

NOTE: The most appropriate and efficient method for diagnosing porphyria is dependent on the types of porphyria encountered within a particular country and the nature of the symptoms experienced. This page is directed at South African patients seeking testing. The recommended approach in other countries will differ.

WHICH FORM OF TESTING IS APPROPRIATE FOR YOU?

There is no single answer for everyone, as the answer varies according to your symptoms, your family history and where you live. In South Africa, most people with porphyria have a single type of porphyria (variegate porphyria), which makes testing somewhat simpler. The suggestions which follow are therefore directed at South African patients: and visitors to this site who live in other countries should contact their local porphyria authorities.

South African patients with suspected variegate porphyria should read the following page: Variegate porphyria: right or wrong diagnosis?

Group 1: if ALL the following apply:

• You have a family history.
• The type of porphyria in your family is definitely established as variegate porphyria .
• The mutation in your family has been identified as the common mutation.

Then the quickest route to a diagnosis is to be tested for the R59W mutation (a DNA test). If positive, then you have inherited variegate porphyria yourself. If negative, then you have definitely not inherited porphyria.

Group 2: if ALL the following apply:

• You yourself have no symptoms of porphyria.
• You believe you have a family history.
• But you are not absolutely certain which form it is.
• And you are not certain whether the R59W mutation is present in your family.

Then you should do the following:

• Contact those family members though to have porphyria for more details. If they were tested before 1998, we strongly suggest that you encourage them to be retested, since improved testing, including DNA testing, was only available after that date.
• Submit a urine sample and a blood sample to a laboratory for testing.

The following tests should be done:

1. Urine ALA and PBG measurement (this helps to exclude acute intermittent porphyria).
2. Plasma fluorescence scan (this helps to exclude several porphyrias, including variegate porphyria and porphyria cutanea tarda).
3. Erythrocyte fluorescence (this helps to exclude erythropoietic protoporphyria and congenital erythropoietic porphyria).
4. DNA testing for the R59W mutation.

This is a thorough examination which will confidently exclude the common South African form of variegate porphyria, and will also exclude active forms of the other porphyrias. The only possible false-negative results would arise where the family carries a form of porphyria other than variegate porphyria, or a variegate porphyria-associated mutation other than R59W, and the patient himself or herself is not expressing the disease. The only way to identify this rare situation is to have the original family members properly tested and define the nature of the porphyria in them.

Group 3: if you have symptoms you believe may be due to porphyria

Testing is actually easier in this situation, since if your symptoms ARE due to porphyria, then your tests MUST be positive. In general, patients with clinically expressed porphyria also express the disease biochemically at a level easy to detect in the laboratory.

• Submit a urine sample and a blood sample to a laboratory for testing.

The following tests should be done:

1. Urine ALA and PBG measurement (this helps to exclude acute intermittent porphyria, and variegate porphyria in the acute attack).
2. Urine porphyrin screening, followed by chromatographic quantitation if positive, to estimate the activity of acute intermittent porphyria and variegate porphyria, and to confirm porphyria cutanea tarda.
3. Plasma fluorescence scan (this helps to exclude several porphyrias, including variegate porphyria).
4. Erythrocyte fluorescence (this helps to exclude erythropoietic protoporphyria and congenital erythropoietic porphyria).
5. DNA testing for the R59W mutation.
6. If your results are negative, then your symptoms are not due to porphyria, and it is therefore highly unlikely that you in fact have porphyria. Your doctor must in any event help you to find another cause for your symptoms.

Group 4: if your family is known to have a form of porphyria other than variegate porphyria due to the R59W mutation

You should contact us or the laboratory who made the original diagnosis in your family for advice. It may be possible to perform DNA tests specifically directed at the mutation in your family.

WARNING: INCOMPLETE TESTING

Few laboratories are able to perform the complete range of tests as set out here. Incomplete results (e.g. a DNA test without biochemical tests, biochemical screening without plasma scanning, blood tests without urine tests, etc.) may be misleading, and no final answer can be given unless ALL tests have been adequately performed. If you are in doubt, you or your doctor are welcome to ask our advice.

SUBMITTING SAMPLES FOR TESTING

Read the following: Guidelines for the collection and dispatch of samples for testing.