An autopsy case of acute porphyria with a decrease of both uroporphyrinogen I synthetase and ferrochelatase activities

Abstract

An autopsy case of a 37-year-old woman with acute porphyria is reported. The patient began to complain of severe menstrual pains, and later developed serious peripheral neuropathy and various autonomic nervous symptoms. The autopsy revealed a marked loss and degeneration of axons and myelin sheaths in the peripheral nervous system (PNS), and prominent central chromatolysis of the spinal anterior horn cells. The predominant process of the peripheral neuropathy appeared to be axonal degeneration. Biochemical analysis showed a marked increase of delta-aminolevulinic acid (ALA), porphobilinogen, uroporphyrin, and coproporphyrin in the urine, and an increase of coproporphyrin and protoporphyrin in the stools and blood. In the analysis of the enzymatic activities of the liver and bone narrow, the activity of ALA synthetase (ALA-S) was markedly increased, and the activities of both uroporphyrinogen I synthetase (URO-S) and ferrochelatase were decreased. It was characteristic in this case that the enzymatic abnormalities found in both acute intermittent porphyria (AIP) and variegate porphyria (VP) coexisted. Biochemical analysis of the sciatic nerve showed an increase of ALA-S activity and a decrease of both URO-S and ALA dehydrase activities. This was the first report that indicated the presence of abnormal activities of the heme biosynthetic enzymes in the peripheral nerves of porphyric patients. The possibility was discussed that these enzymatic abnormalities of the heme biosynthesis in the peripheral nerve itself might be strongly related to the pathogenesis of the porphyric neuropathy.