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Home > Diagnosing Porphyria > Diagnosis in those with a family history
Diagnosing Porphyria

Patients with a family history

NB The diagnostic algorithms recommended in the pages are designed for patients in the South African context. Approaches will differ for patients in other settings.

This section deals with patients who are themselves asymptomatic but report a family history of porphyria and wish to have themselves tested. In South Africa, over 95% of patients with variegate porphyria (VP) carry a single mutation, the R59W mutation, and screening for the R59W mutation is therefore a sensitive and convenient method of diagnosis provided that the following conditions are met:

  • The family history is genuine, i.e. there really is porphyria in the family
  • The porphyria is variegate porphyria
  • The underlying mutation is indeed R59W.

Proceed as follows.

If Variegate Porphyria is Proven in the Family and Has Been Shown to be R59W Positive

Direct DNA-based testing for the R59W mutation is simple, convenient and 100% sensitive and specific for detecting VP in all relatives.

If Variegate Porphyria Due to a Different Mutation has Already Been Diagnosed in the Family

The most appropriate screening test is again direct DNA-based testing, but this will have to specifically designed to detect the family's mutation. Contact the institution who made the original diagnosis.

If there is Uncertainty About the Original Family History

This applies where one is uncertain about the accuracy of the family history of porphyria, as to whether it was VP and whether the mutation was R59W . In such cases, the patient should essentially be fully screened for all types of porphyria. Submit blood (10ml EDTA— two mauve-topped hematology tubes) and urine 30ml. The following tests are required.

R59W DNA testing

This will detect the common R59W mutation which accounts for most cases of VP in South Africa.

Erythrocyte fluorescence

This will help to detect erythropoietic protoporphyria and congenital erythropoietic porphyria.

Plasma fluorescence scan

This is a valuable screening test for variegate porphyria, acute intermittent porphyria and porphyria cutanea tarda.

Urine screening and quantitation

Urine screening and chromatographic analysis of ALA, PBG and porphyrin concentrations are necessary for the diagnosis of acute intermittent porphyria and porphyria cutanea tarda, and will also provide useful information about disease activity whichever porphyria is present.