Why do the acute hepatic porphyrias produce abdominal pain, psychiatric disturbance, and motor neuropathy, whereas pure cutaneous porphyrias such as porphyria cutanea tarda never cause these neurological features?

• A The acute porphyria enzyme defects occur inside neurons themselves
• B Neuronal mitochondria selectively accumulate protoporphyrin IX in all porphyrias
• C Cutaneous porphyrins are unable to cross the peripheral nerve sheath
• D Only the acute porphyrias allow delta-aminolevulinic acid, a GABA-like neurotoxin, to accumulate ✓

Explanation

Enzyme blocks proximal to porphobilinogen, seen in the acute hepatic porphyrias, cause accumulation of delta-aminolevulinic acid, which structurally resembles GABA and interferes with neurotransmitter release, explaining abdominal pain, seizures, psychosis, and neuropathy. Blocks distal to ALA, as in porphyria cutanea tarda, raise only photoactive porphyrins and spare the nervous system entirely. The defects are expressed in the liver, not neurons, and neuronal protoporphyrin deposition is not the mechanism.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.