Active = symptomatic PPOX heterozygotes; ALA = δ-aminolevulinic acid; Asx = asymptomatic PPOX heterozygotes; NI = not increased; PBG = porphobilinogen; PPOX = protoporphyrinogen oxidase

This enzyme oxidizes protoporphyrinogen to protoporphyrin and its deficiency leads to accumulation of protoporphyrinogen in the liver, which subsequently is autoxidized to protoporphyrin.

The enzyme assay is not needed for diagnostic purposes and is not widely available.

PBG elevation should be detected by a quantitative method such as that described by Mauzerall & Granick [1956] which also measures ALA or mass spectrometry. Results of qualitative methods such as the Watson-Schwartz and Hoesch tests, which are considered obsolete, should be confirmed on the same sample by a quantitative method. ALA is less elevated than PBG. Note: ALA is elevated in ALAD porphyria (ADP), in which PBG is normal or only slightly increased.

Active VP is suggested by a quantitative PBG that is substantially elevated.

For screening, it is also useful to measure total porphyrins in the same urine sample, since levels of PBG can be less elevated in VP and HCP than in AIP and decrease to normal more rapidly. Note: Unlike a substantial increase in PBG, a substantial increase in urinary porphyrins does not indicate porphyria, as urinary porphyrins are increased in many other medical conditions, especially when the hepatobiliary system or bone marrow is affected.

PBG and total porphyrins may not be elevated in persons whose symptoms have resolved. If an acute porphyria is suspected to have caused past symptoms, full biochemical testing to include urinary ALA, PBG, and porphyrins, fecal porphyrins, and plasma porphyrins may be indicated.

Fecal porphyrins are markedly elevated in HCP and VP, whereas in AIP there is little or no elevation. The pattern of fecal porphyrins differentiates HCP and VP, with marked predominance of coproporphyrin III in HCP, and roughly equal elevations of coproporphyrin III and protoporphyrin in VP.

A fluorescence scan of diluted plasma at neutral pH provides a fluorescence peak at wavelength ~626 nm in VP that is highly sensitive and specific for this porphyria [Poh-Fitzpatrick 1980]. This is the most sensitive biochemical method for establishing VP in the absence of symptoms. Fecal porphyrin analysis is somewhat less sensitive than plasma fluorescence scanning.