Acute intermittent porphyria (AIP) is caused by porphobilinogen deaminase (HMBS) deficiency. Why do AIP attacks not cause photosensitivity despite other porphyrias causing it?

• A In AIP, ALA and PBG accumulate but do not form porphyrins, which are the photosensitising compounds ✓
• B AIP attacks only occur nocturnally so sunlight exposure is absent
• C AIP involves liver porphyrin accumulation which does not reach the skin
• D PBG is rapidly excreted renally before reaching the skin

Explanation

Photosensitivity in porphyrias occurs when porphyrins (cyclic tetrapyrroles) accumulate in the skin and absorb UV/visible light, generating reactive oxygen species and causing phototoxic damage. In AIP, the enzymatic block is at HMBS (uroporphyrinogen I synthase), causing accumulation of ALA and PBG — linear (non-cyclic) porphyrin precursors. These are not porphyrins and do not absorb light in the photosensitising range. They are neurotoxic, causing the neuropsychiatric and abdominal manifestations. Porphyrias with distal blocks (PCT, EPP, VP, HCP) accumulate cyclic porphyrins/porphyrinogens and therefore cause photosensitivity. Option D is a contributing factor but not the explanation for absent photosensitivity.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.