Acute intermittent porphyria (AIP) causes acute neurovisceral attacks. Which of the following correctly describes the enzyme defect and the compound accumulating to toxic levels?

• A Deficiency of ALA dehydratase → accumulation of ALA and protoporphyrin IX causing photosensitivity and neurological symptoms
• B Deficiency of ferrochelatase → accumulation of protoporphyrin IX in erythrocytes and liver causing erythropoietic protoporphyria
• C Deficiency of uroporphyrinogen decarboxylase → accumulation of uroporphyrin III causing porphyria cutanea tarda
• D Deficiency of uroporphyrinogen I synthase (HMB synthase) → accumulation of porphobilinogen (PBG) and delta-aminolevulinic acid (ALA), which are neurotoxic ✓

Explanation

Acute intermittent porphyria results from autosomal dominant partial deficiency of hydroxymethylbilane synthase (HMBS, also called uroporphyrinogen I synthase or PBG deaminase). The block causes accumulation of porphobilinogen (PBG) and its precursor delta-aminolevulinic acid (ALA). ALA is structurally similar to GABA and is neurotoxic (inhibits Na⁺-K⁺-ATPase, impairs GABA signaling). AIP characteristically has no photosensitivity (as porphyrins do not accumulate). ALA dehydratase deficiency is extremely rare. Ferrochelatase deficiency causes EPP. PCT involves URO-decarboxylase.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.