A 30-year-old woman presents with acute attacks of abdominal pain, autonomic dysfunction, and peripheral neuropathy after starting an oral contraceptive pill. Urine is dark red. The enzyme deficient in this condition is:
- A Uroporphyrinogen III cosynthase, causing congenital erythropoietic porphyria (Gunther's disease)
- B Porphobilinogen deaminase (hydroxymethylbilane synthase), causing acute intermittent porphyria (AIP) ✓
- C Uroporphyrinogen decarboxylase, causing porphyria cutanea tarda (PCT)
- D Ferrochelatase, causing erythropoietic protoporphyria (EPP)
Correct answer: B. Porphobilinogen deaminase (hydroxymethylbilane synthase), causing acute intermittent porphyria (AIP)
Explanation
Acute intermittent porphyria (AIP) is caused by 50% deficiency of porphobilinogen (PBG) deaminase. Precipitants (OCP, barbiturates, alcohol, fasting) upregulate ALA synthase-1, overwhelming the reduced PBG deaminase capacity. ALA and PBG accumulate; ALA is neurotoxic (structurally similar to GABA), causing acute neurovisceral crises. Urine darkens from PBG oxidation to porphyrins on standing. AIP never causes cutaneous photosensitivity (unlike PCT or EPP), because ALA and PBG are not photosensitising.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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