title: The hepatic lesion in protoporphyria (PP): preliminary studies of haem metabolism, liver structure and ultrastructure.
abstract: Five unrelated patients with protoporphyria (PP) had diagnostic liver biopsies performed to assess the degree of liver damage. The porphyrin content of the liver was quantitated and characterized and liver damage was assessed. Ultraviolet (UV) microscopy was performed in each case. Liver structure was assessed by light, polarization and electron microscopy. In 3 patients the liver was visualized directly before biopsy through a peritoneoscope. Liver damage ranged from minimal cell necrosis to portal fibrosis; the latter was observed in a 27-year-old sib of a patient (M.I.) who had died, aged 29, 3 years previously in liver failure from PP-related cirrhosis. Liver tissue from the latter patient which was obtained at the time of autopsy was re-examined by light and polarization microscopy. Hepatic pigment deposits, thought to be lipofuscin, showed birefringence on polarization microscopy in two cases, one of them being patient M.I. with PP-cirrhosis. Liver fluorescence on UV microscopy was centrizonal, punctate, faded rapidly and was easily distinguishable from that seen in porphyria cutanea tarda (PCT). The porphyrin content of the liver tissue in biopsied patients was between 5 mug and 80 mug, and in the autopsy case 1600 mug protoporphyrin/g wet weight liver, and on thin layer chromatography only dicarboxylic porphyrins were demonstrable. Hepatic cytochrome P-450 levels in protoporphyria were within normal range. Vmax and Km for aminopyrine-N-demethylation and benzpyrene hydroxylation did not differ significantly from our findings in PCT, variegate porphyria in remission and in non-porphyric controls. However, the activity of hepatic delta-aminolaevulinic acid (ALA) synthetase was significantly enhanced in 2 of the 3 patients in whom this measurement was performed.
mesh_terms: D000328:Adult; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008859:Microscopy, Polarization; D011164:Porphyrias / Q000378:metabolism / Q000473:pathology; D011166:Porphyrins / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism
chemical_list: D011166:Porphyrins; D011524:Protoporphyrins; D006418:Heme; D003577:Cytochrome P-450 Enzyme System