A 35-year-old man presents with acute abdominal pain, neuropsychiatric symptoms, and dark port-wine urine after starting phenobarbital. Urine Watson-Schwartz test is positive for porphobilinogen (PBG). The diagnosis is acute intermittent porphyria (AIP). The enzyme deficient is:
- A ALA synthase (ALAS1)
- B Uroporphyrinogen III synthase
- C Porphobilinogen deaminase (PBGD/HMB synthase) — 50% reduced activity ✓
- D Ferrochelatase
Explanation
Acute intermittent porphyria is caused by autosomal dominant 50% deficiency of porphobilinogen deaminase (PBGD, also called hydroxymethylbilane synthase/HMBS), the third enzyme in heme synthesis that converts 4 PBG molecules to hydroxymethylbilane. During attacks (precipitated by CYP-inducing drugs like barbiturates, fasting, stress — all of which upregulate ALAS1), the increased ALA and PBG flux overwhelms the reduced PBGD activity, causing PBG and ALA accumulation. Classic triad: abdominal pain, neuropsychiatric features, autonomic instability. Key: urine turns dark on standing (oxidized porphobilinogen). Treatment: hemin infusion (suppresses ALAS1 via feedback), IV glucose, avoid precipitants.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.