A 35-year-old woman presents with episodic severe abdominal pain, neuropsychiatric symptoms, and dark urine after taking sulfonamides. Urine porphobilinogen (PBG) is markedly elevated during attacks. The enzyme deficient in this condition and the pathway it normally catalyses is:

• A Hydroxymethylbilane synthase (PBG deaminase) — condenses 4 PBG molecules into HMB ✓
• B Uroporphyrinogen III synthase — converts HMB to uroporphyrinogen III
• C ALA dehydratase — condenses 2 ALA molecules into PBG
• D Ferrochelatase — inserts Fe2+ into protoporphyrin IX

Explanation

Acute intermittent porphyria (AIP) is caused by autosomal dominant partial deficiency of hydroxymethylbilane synthase (also called PBG deaminase or uroporphyrinogen I synthase). This enzyme polymerises 4 molecules of PBG into the linear tetrapyrrole hydroxymethylbilane (HMB). Deficiency causes accumulation of PBG and ALA which are neurotoxic, explaining the neuropsychiatric and autonomic (abdominal pain) features. Attacks are precipitated by drugs inducing ALA synthase (sulfonamides, barbiturates). Urine turns dark on standing due to porphobilin formed from PBG oxidation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.