Acute intermittent porphyria (AIP) presents with abdominal pain, neuropsychiatric features, and autonomic dysfunction but NO skin photosensitivity. The enzymatic defect is in porphobilinogen deaminase (PBGD). Why is there no photosensitivity in AIP?

• A AIP occurs only in the liver, so porphyrins do not accumulate in skin
• B The block is early in the pathway (before uroporphyrinogen); ALA and PBG accumulate, but these non-porphyrin precursors are water-soluble, non-photoactive, and excreted in urine before reaching skin ✓
• C AIP is associated with reduced haem synthesis so less porphyrin is produced overall
• D ALA and PBG are converted to melanin, which provides photoprotection

Explanation

In AIP, the block at PBGD (hydroxymethylbilane synthase) causes accumulation of the early precursors ALA (delta-aminolevulinic acid) and PBG (porphobilinogen). Crucially, ALA and PBG are not porphyrins — they lack the cyclic tetrapyrrole ring required for visible light absorption at 400 nm (Soret band). Being water-soluble, they are rapidly cleared into the urine. Photosensitivity in porphyrias (e.g., PCT, EPP, CEP) is caused by accumulated porphyrins or metalloporphyrins (cyclic tetrapyrroles) in skin that absorb light and generate singlet oxygen. Since AIP blocks conversion of PBG to hydroxymethylbilane (a linear tetrapyrrole), cyclic porphyrins do not accumulate in skin.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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