title: Transient erythropoietic protoporphyria associated with chronic hepatitis and cirrhosis in a cohort of German shepherd dogs.
abstract: Over the course of one year, slight jaundice and ascites suggestive of chronic liver disease occurred in 17 German shepherd dogs from one breeding colony. Blood analyses, performed twice with a six-month interval, revealed elevated serum activities of liver enzymes in 13 dogs. In addition, four young adult German shepherd dogs that showed severe ascites, slight jaundice and increased serum liver enzyme activities were referred for further evaluation. Because of their poor prognosis these four dogs were euthanased. There were no signs of photosensitivity. Postmortem examinations revealed macronodular darkened livers, which were characterised histopathologically by cirrhosis associated with aggregates of brown pigments showing a striking orange birefringence in polarised light. Ultrastructurally, the crystalline pigments were typical of protoporphyrins. High-performance liquid chromatographic analysis of liver samples revealed very high levels of protoporphyrins (mean 9550 nmol/g wet liver, reference value 0.41 nmol/g wet liver) and low activities of ferrochelatase (mean 0.274 mmol/mg protein/hour, reference value 0.684 nmol/mg protein/hour). Twenty-six months after the onset of the hepatopathies, the clinical condition of the 13 surviving dogs had improved and their serum liver enzyme activities were normal. The clinical histories and pedigree analyses were not in concordance with an inherited form of protoporphyria. There was no known history of exposure to toxic substances or drugs. The findings are in accordance with a transient erythropoietic protoporphyria associated with hepatic complications, presumably caused by exposure to a porphyrinogenic, ferrochelatase-inhibitory substance of unknown origin.
authors.affiliation: Pathology Division, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 8, 3584 CM Utrecht, The Netherlands.
authors.forename: E J B Veldhuis
authors.initials: EJ
authors.lastname: Kroeze
authors.forename: J
authors.initials: J
authors.lastname: Zentek
authors.forename: A
authors.initials: A
authors.lastname: Edixhoven-Bosdijk
authors.forename: J
authors.initials: J
authors.lastname: Rothuizen
authors.forename: T S G A M
authors.initials: TS
authors.lastname: van den Ingh
mesh_terms: D000818:Animals; D001947:Breeding; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D004283:Dog Diseases / Q000473:pathology*; D004285:Dogs; D005260:Female; D005294:Ferrochelatase / Q000378:metabolism*; D006521:Hepatitis, Chronic / Q000150:complications / Q000473:pathology / Q000662:veterinary*; D008099:Liver / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000473:pathology / Q000662:veterinary*; D008297:Male; D046351:Protoporphyria, Erythropoietic / Q000150:complications / Q000473:pathology / Q000662:veterinary*; D011524:Protoporphyrins / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D011524:Protoporphyrins; D005294:Ferrochelatase