The neurological manifestations of porphyria: a review.
The hereditary hepatic porphyrias, PV, AIP and HC, are characterized biochemically by increased excretion of porphyrins and the porphyrin precursors ALA and PBG. They are characterized clinically by episodes of acute neurological involvement. The increased production of porphyrins and porphyrin precursors has been shown to be due to partial enzyme blocks along the heme biosynthetic pathway which results in secondary depression of the key enzyme ALA-synthetase. The neurological manifestations could therefore be related to either a decrease in essential heme-proteins or other heme-containing compounds within the nervous system, or to a toxic effect of the over-production of the porphyrin precursors ALA and PBG. There is evidence for and against both theories. Recent work from a number of research groups has shown the porphyrin precursors to have potent pharmacological effects on the nervous system, and these are possibly related to the GABA receptor and binding site-porphyrin precursor interactions. Current studies on therapy of the acute attack have concentrated on suppression of ALA-synthetase activity, and consequently, on reduced ALA and PBG production. A number of such methods of therapy have met with remarkable success and hold promise for the future treatment of the acute attack.
D000208:Acute Disease; D000622:Aminolevulinic Acid / Q000378:metabolism; D000818:Animals; D006418:Heme / Q000096:biosynthesis; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000150:complications* / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009420:Nervous System / Q000187:drug effects; D009461:Neurologic Manifestations; D010525:Peripheral Nerves / Q000473:pathology; D011162:Porphobilinogen / Q000378:metabolism; D011164:Porphyrias / Q000150:complications* / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D011166:Porphyrins / Q000378:metabolism / Q000494:pharmacology
D011166:Porphyrins; D006418:Heme; D011162:Porphobilinogen; D000622:Aminolevulinic Acid