July 14, 2020
Porphyria Minimize


The porphyrias are usually considered a difficult category of diseases as they are rare and because there appears to be no apparent explanation for the symptomatology from the biochemical pathways. Despite this, the diagnosis can only be made if there is a high index of suspicion with all cases of photosensitivity, abdominal pain and unexplained nervous systems disorders eg status epilepticus and encephalopathies.

The porphyrias can be classified into those disorders causing acute crises, photosensitivity or a mixture. Photosensitivity may present either as acute painful swelling of the exposed skin or as fragility of exposed skin. This latter feature may appear as repeated tears on minimal trauma, easy bruising or multiple tiny scars.

If an acute porphyria is suspected, urine samples should be taken for urgent analysis of PBG, d-ALA and total porphyrins. Porphyrins are stable in light protected containers. Since an accurate diagnosis is essential and porphyrins are relatively rarely assayed in most routine laboratories, it is recommended that a specialist laboratory is approached.

Clinical presentation of the porphyrias


Porphyrias causing acute or neurological crises

Porphyrias causing mixed symptomatology

Porphyrias causing photosensitivity


Acute intermittent porphyria

Variegate porphyria,
Hereditary coproporphyria

Congenital erythropoetic porphyria,
Porphyria cutanea tarda,
Erythropoetic protoporphyria


acute crises characteristically cause abdominal pain but neuro-psychiatric Disturbances including status epilepticus, unexplained encephalopathy, mood disturbances and peripheral neuropathies may be presenting features

Acute and neuro-psychiatric symptoms are the usual presenting features. Photosensitivity (30%) may mimic PCT or may be present only during acute episode

Patients with EPP are likely to exhibit classical photosensitivity with painful swollen reddening of exposed skin, whereas PCT patients may only show pigmentation &/or scars in a 'photo' distribution ie on malar regions of the face and backs of the hands


random urine sample for urgent analysis of PBG and d-ALA to confirm the presence of an acute porphyria

during remission send urine stool samples in light protected container

during acute episode send random urine for PBG and d-ALA

send urine & stool samples in light protected container if EPP is suspected send heparin/EDTA blood sample (notify laboratory)

Investigations appropriate for symptoms



Diagnostic test

Acute attack

Acute intermittent porphyria

PBG and d-ALA markedly (ie > 10 fold) raised during an attack and are characteristically raised during remission.

Patients have reduced activity of erythrocyte PBG deaminase (but only a proportion of gene carriers develop clinical disease)

Acute attack

Variegate porphyria

Increased stool protoporphyrin

Characteristic plasma fluorescence @ 626 nm

Acute attack

Hereditary coproporphyria

Increased stool coproporphyrin III and no increase in stool protoporphyrin

Fragility of exposed skin

Porphyria cutanea tarda

Increased urinary uroporphyrin and stool isocoproporphyrin

Acute pain on exposure of skin to sunlight

Congenital erythropoetic porphyria

Massively increased uroporphyrin I

Acute pain on exposure of skin to sunlight

Erythropoetic protoporphyria

Increased erythrocyte free protoporphyrin

Reduced lymphocyte ferrochelatase activity

If uncertain it is best to take samples of plasma, urine and stool. Specimens for acute porphyrias may only be abnormal during an acute episode. All samples should be protected from light.

Porphyria cutanea tarda

PCT is likely to be due to the coincidental association of several factors including liver toxins/disease and iron overload. A relationship with heterozygosity of the HFE haemochromatosis gene has been reported. In the past, the hepatic damage was usually alcohol, however, nowadays in Western Europe, the majority of cases of PCT appear to be associated with hepatitis C and all patients should be tested for this.

Secondary porphyrias

Increased excretion of porphyrins in the urine and stools are seen in association with other disorders eg tyrosinaemia, lead poisoning, iron deficiency and alcoholism.

Symptoms similar to an acute attack may occur with lead poisoning and tyrosinaemia but in these cases the urine contains excess d-ALA but no PBG.

Drugs associated with porphyria

The lists of drugs safe to use or essential to avoid is continually being revised and up to date information can be obtained from the following porphyria internet sites:




  • Elder GH. Worwood M. Mutations in the hemochromatosis gene, porphyria cutanea tarda, and iron overload. Hepatology. 1998;27:289-91.

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