Porphyria
The porphyrias are inherited or acquired defects of heme biosynthesis enzymes that cause toxic accumulation of porphyrin precursors, splitting into acute hepatic porphyria (neurovisceral attacks with no photosensitivity, confirmed by elevated urinary porphobilinogen) and porphyria cutanea tarda (blistering photosensitivity from elevated urinary uroporphyrins). Acute attacks are treated with IV hemin and glucose loading, while porphyria cutanea tarda responds to phlebotomy or low-dose hydroxychloroquine.
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What this article covers
- Overview
Definition: the porphyrias are hereditary or acquired conditions caused by defective activity of a specific heme-biosynthesis enzyme, causing accumulation of the precursor upstream of the block.
- Epidemiology
AIP: autosomal dominant with low penetrance, so most gene carriers stay clinically silent for life; expression requires a trigger, and symptomatic attacks are more common in women, typically after puberty.
- Risk factors
Cytochrome P450-inducing drugs precipitate acute attacks: sulfonamides, barbiturates, other CYP450 inducers, antipsychotics, and alcohol upregulate ALA synthase and provoke an AIP attack in a susceptible carrier.
- Pathophysiology
Heme synthesis is blocked at a specific enzyme step: each porphyria corresponds to deficient activity of one pathway enzyme, so the precursor immediately upstream of the block accumulates.
- Clinical features
AIP acute attack, the 5 P's: painful abdomen (colicky, moderate to severe, lasting hours to days, no peritoneal signs), port wine-colored urine (darkens on standing), polyneuropathy (motor greater…
- Differential diagnosis
Acute abdomen (appendicitis, cholecystitis, bowel obstruction): true surgical disease shows peritoneal signs, fever, or imaging of an obstructing/inflamed viscus, all absent in a porphyric attack…
- Diagnosis
Acute hepatic porphyria is confirmed by a markedly elevated urinary PBG, with ALA also elevated, measured during the symptomatic attack because levels normalize between episodes; a normal PBG during…
- Management
Acute attack, stabilize and remove precipitants first: discontinue all CYP450-inducing and other porphyrinogenic drugs and treat any underlying infection.
- Complications
Respiratory failure from ascending motor neuropathy: severe AIP attacks can progress to bulbar and diaphragmatic weakness requiring mechanical ventilation, the most dangerous acute complication.
- Prognosis
AIP attacks resolve with prompt treatment: most improve within days of hemin and glucose therapy and precipitant removal, though motor neuropathy can take months to fully recover.
- Prevention
Avoid known precipitants in AIP carriers: strict avoidance of CYP450-inducing drugs (barbiturates, many anticonvulsants, sulfonamide antibiotics, certain antipsychotics) and alcohol, plus adequate…
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