A 32-year-old woman presents with recurrent episodes of acute abdominal pain, psychiatric symptoms, and motor neuropathy triggered by fasting and oral contraceptive pills. Urine turns dark on standing. Urine aminolevulinic acid (ALA) and porphobilinogen (PBG) are markedly elevated. Which enzyme is deficient?
- A ALA synthase (ALAS1)
- B Porphobilinogen deaminase (hydroxymethylbilane synthase) ✓
- C Uroporphyrinogen III synthase
- D Uroporphyrinogen decarboxylase
Explanation
Acute intermittent porphyria (AIP) is caused by deficiency of porphobilinogen (PBG) deaminase (also called hydroxymethylbilane synthase), the third enzyme in heme synthesis. PBG and ALA accumulate and are excreted in urine. PBG is responsible for the neurovisceral manifestations through neurotoxicity and neuroendocrine disruption. Triggers (fasting, OCP, drugs inducing CYP enzymes) increase hepatic ALAS1 demand, overwhelming the enzyme bottleneck. Urine turns dark on standing due to non-enzymatic oxidation of porphyrin precursors. Uroporphyrinogen III synthase deficiency causes congenital erythropoietic porphyria with photosensitivity, not acute attacks.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.