A patient presents with acute abdominal pain, peripheral neuropathy, and red-brown urine precipitated by sulphonamide use. Urine shows markedly elevated ALA and PBG. The diagnosis is Acute Intermittent Porphyria (AIP). The enzyme deficient in AIP is:

• A Porphobilinogen deaminase (PBGD / HMB synthase) — causing ALA and PBG accumulation ✓
• B ALA synthase (ALAS) — the rate-limiting enzyme of haem synthesis
• C Uroporphyrinogen decarboxylase — causing porphyria cutanea tarda
• D Ferrochelatase — causing erythropoietic protoporphyria

Explanation

AIP (autosomal dominant) is caused by ~50% deficiency of PBGD (also called HMB-synthase), which normally polymerises 4 PBG molecules to hydroxymethylbilane. The block causes ALA and PBG to accumulate proximally. Precipitation by drugs (sulphonamides, barbiturates, OCP) that induce hepatic ALAS1 increases substrate flux beyond the deficient PBGD capacity. Accumulated ALA (a GABA analogue) is neurotoxic, causing autonomic dysfunction, peripheral neuropathy, and psychiatric symptoms. Urine turns red on standing (PBG oxidises to porphyrins). Haem arginate suppresses ALAS1.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.