Pathogenesis of Neural Manifestations in Acute Porphyria

At least 4 possible mechanisms may be postulated to explain the neural manifestations of acute porphyria in the hereditary hepatic porphyrias. These are (i) excessive amounts of porphyrins or porphyrin precursors produced in the liver during acute attacks are transported to the central and peripheral nervous system, where they exert neurotoxic effects; (ii) unidentified metabolites of the aforementioned compounds may be responsible; (iii) in patients with these diseases there may be a metabolic defect in neural haem biosynthesis which is aggravated by precipitating factors, thereby leading to acute neural manifestations; and (iv) the hepatic and nervous system lesions may be metabolically quite unrelated. Each of these possibilities is considered, and evidence is adduced that a genetic defect in haem biosynthesis in the nervous system is the most plausible hypothesis.