Acute intermittent porphyria is caused by deficiency of which enzyme?

• A. Uroporphyrinogen decarboxylase
• B. Porphobilinogen deaminase
• C. ALA synthase
• D. Ferrochelatase

Answer: (B)

Acute intermittent porphyria arises when the enzyme that converts porphobilinogen to hydroxymethylbilane in the heme synthesis pathway is deficient. This block leads to buildup of neurotoxic precursors, especially delta-aminolevulinic acid and porphobilinogen, which drive the characteristic neurovisceral attacks: severe abdominal pain, autonomic symptoms, and sensory–motor neuropathies. Unlike some other porphyrias that prominently affect the skin, this form mainly presents with neurologic and visceral symptoms. Other enzyme defects in the pathway produce different clinical pictures (for example, uroporphyrinogen decarboxylase deficiency causes porphyria cutanea tarda with photosensitivity; ferrochelatase deficiency causes erythropoietic protoporphyria; ALA synthase deficiency would alter the initial steps of the pathway). Thus, the deficiency in porphobilinogen deaminase best explains acute intermittent porphyria.