A 30-year-old woman presents with recurrent episodes of severe abdominal pain, peripheral neuropathy, and confusion, precipitated by oral contraceptives. Urine turns dark on standing. Urine porphobilinogen (PBG) is markedly elevated. Which enzyme is deficient?
- A ALA dehydratase (PBGS) — causing ALA accumulation
- B Porphobilinogen deaminase (PBGD/HMBS) — causing PBG and ALA accumulation — acute intermittent porphyria (AIP) ✓
- C Uroporphyrinogen decarboxylase — causing uroporphyrin accumulation — porphyria cutanea tarda (PCT)
- D Ferrochelatase — causing protoporphyrin IX accumulation — erythropoietic protoporphyria (EPP)
Explanation
Acute intermittent porphyria (AIP) results from ~50% deficiency of PBG deaminase (HMBS), the third enzyme of heme synthesis. Precipitants (drugs inducing ALA synthase-1 via CYP450 induction — including OCP estrogens — alcohol, fasting) increase demand for heme and upregulate ALAS1, but the partial enzyme block causes ALA and PBG accumulation. ALA is neurotoxic (GABA receptor agonist), explaining the neurovisceral symptoms. Urine darkens on standing due to PBG oxidation to porphobilin and uroporphyrin. Treatment: haem arginate (suppresses ALAS1) and glucose (carbohydrate loading). PCT presents with photosensitive blistering skin lesions.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.