First-Line Tests

No single test is effective for screening all Porphyrias. However, one or two tests can be relied upon in almost all situations, depending on the symptoms. Information about screening tests is summarized in Table 2 below.

The symptoms of Porphyrias are due to effects on the nervous system, the skin, or both. Acute Porphyrias lead to a variety of effects on the nervous system such as abdominal pain, nausea, vomiting, pain in the extremities and elsewhere, muscle weakness and altered mental functioning. Cutaneous Porphyrias lead to skin manifestations in sun-exposed areas (photosensitivity). These may include chronic blistering or more acute pain and swelling. Some Porphyrias have both cutaneous and neurological manifestations.

Acute Porphyrias. Measurement of porphobilinogen (PBG) in urine can be relied upon for screening for the acute Porphyrias when there are neurological symptoms such as abdominal pain. PBG is markedly increased in almost all patients with symptoms of acute Porphyria and is never markedly increased in diseases other than acute Porphyria. Therefore this test is both sensitive and specific.

Measurement of PBG is often combined with delta-aminolevulinic acid (ALA) and total urine porphyrins. ALA is increased, but PBG is not, in ALAD Porphyria (ADP), the most rare form of acute Porphyria. In some patients with acute Porphyria, urinary porphyrins may remain increased longer than ALA and PBG. But it must be remembered that increases in urinary porphyrins occur in other medical conditions, and are therefore much less specific than increases in ALA and PBG. In urgent situations, PBG can be measured immediately (as a STAT test) and the urine sample saved for later measurement of ALA and total porphyrins.

If urine ALA, PBG and total porphyrins are normal, it is quite certain that any recent symptoms are not due to an acute Porphyria. If these are markedly increased, further testing is needed to determine specific type of Acute Hepatic Porphyria. An isolated increase in urine porphyrins (especially coproporphyrin) is nonspecific and therefore does not always require further testing.

Cutaneous Porphyrias. Measuring total plasma porphyrins is effective for screening patients with skin photosensitivity, because the value can be expected to be very much increased in any patient with skin manifestations due to Porphyria. Plasma porphyrins are seldom increased in other medical conditions.

If this test is normal, cutaneous Porphyrias that cause blistering skin lesions are effectively excluded. Further testing is needed if total plasma porphyrins are increased to determine specific type of Porphyria. But although this is a highly effective screening test, in that it is both sensitive and specific, it is less sensitive than an erythrocyte protoporphyrin determination in detecting Erythropoietic Protoporphyria (EPP).

Table 2. First-line testing for patients in whom Porphyria is suspected as a cause of either neurological symptoms or photosensitivity.