A 32-year-old woman presents with recurrent episodes of severe abdominal pain, peripheral motor neuropathy, and psychiatric symptoms precipitated by oral contraceptive pill use. Urine porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) are markedly elevated during attacks. The enzyme deficiency responsible is:

• A Uroporphyrinogen decarboxylase
• B ALA dehydratase
• C Ferrochelatase
• D PBG deaminase (hydroxymethylbilane synthase) — acute intermittent porphyria ✓

Explanation

Acute intermittent porphyria (AIP) is caused by haploinsufficiency of PBG deaminase (hydroxymethylbilane synthase), the third enzyme in heme synthesis. When hepatic heme synthesis is upregulated by drugs (OCP, barbiturates, alcohol), the reduced PBG deaminase becomes rate-limiting, causing ALA and PBG accumulation. Both ALA and PBG are directly neurotoxic, explaining the neurovisceral symptoms. Urine darkens on standing (PBG oxidizes to porphobilin, then uroporphyrin). Treatment includes IV hemin (suppresses ALA synthase-1 via heme feedback) and high-glucose infusion. OCP-containing progestogens strongly induce CYP3A4 and ALAS1.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.