Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1982 Mar;34(2):322–330.

Bovine protoporphyria: documentation of autosomal recessive inheritance and comparison with the human disease through measurement of heme synthase activity.

J R Bloomer, K O Morton, R J Reuter, G R Ruth
PMCID: PMC1685290  PMID: 7072720

Abstract

Protoporphyria is an autosomal dominant disease in man in which protoporphyrin accumulated because of a defect in heme synthase (ferrochelatase) activity. A disease has been described in cattle that has the same manifestations as does the human disease. We measured heme synthase activity in sonicates of cultured skin fibroblasts and whole liver homogenates from animals with protoporphyria, their unaffected parents, and normal cattle in order to examine the mode of inheritance and compare it with human protoporphyria. The mean activity (+/- SEM) in fibroblasts from the three groups was 2.0 +/- 0.4, 47 +/- 12, and 149 +/- 10 pmol heme formed/mg protein per hr, respectively, consistent with autosomal recessive inheritance. Similarly, the levels of heme synthase activity in livers of the parents were intermediate to those of normal animals and of animals with protoporphyria. When compared with normal human fibroblasts and liver, the specific activity of heme synthase in normal bovine tissue was significantly higher. These studies indicate that manifestations of protoporphyria do not occur in cattle unless the animal is homozygous for the gene defect, whereas in humans, the heterozygous condition is sufficient. This is probably because the specific activity of heme synthase in cells of heterozygous animals is not reduced to a level that significantly alters heme metabolism.

Full text

PDF
322

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Becker D. M., Viljoen J. D., Katz J., Kramer S. Reduced ferrochelatase activity: a defect common to porphyria variegata and protoporphyria. Br J Haematol. 1977 Jun;36(2):171–179. doi: 10.1111/j.1365-2141.1977.tb00637.x. [DOI] [PubMed] [Google Scholar]
  2. Bloomer J. R., Bonkowsky H. L., Ebert P. S., Mahoney M. J. Inheritance in protoporphyria. Comparison of haem synthetase activity in skin fibroblasts with clinical features. Lancet. 1976 Jul 31;2(7979):226–228. doi: 10.1016/s0140-6736(76)91027-8. [DOI] [PubMed] [Google Scholar]
  3. Bloomer J. R., Brenner D. A., Mahoney M. J. Study of factors causing excess protoporphyrin accumulation in cultured skin fibroblasts from patients with protoporphyria. J Clin Invest. 1977 Dec;60(6):1354–1361. doi: 10.1172/JCI108895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bloomer J. R. Characterization of deficient heme synthase activity in protoporphyria with cultured skin fibroblasts. J Clin Invest. 1980 Feb;65(2):321–328. doi: 10.1172/JCI109675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bloomer J. R. Enzyme defects in the porphyrias and their relevance to the biochemical abnormalities in these disorders. J Invest Dermatol. 1981 Jul;77(1):102–106. doi: 10.1111/1523-1747.ep12479280. [DOI] [PubMed] [Google Scholar]
  6. Bonkowsky H. L., Bloomer J. R., Ebert P. S., Mahoney M. J. Heme synthetase deficiency in human protoporphyria. Demonstration of the defect in liver and cultured skin fibroblasts. J Clin Invest. 1975 Nov;56(5):1139–1148. doi: 10.1172/JCI108189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bottomley S. S., Tanaka M., Everett M. A. Diminished erythroid ferrochelatase activity in protoporphyria. J Lab Clin Med. 1975 Jul;86(1):126–131. [PubMed] [Google Scholar]
  8. Brenner D. A., Bloomer J. R. The enzymatic defect in variegate prophyria. Studies with human cultured skin fibroblasts. N Engl J Med. 1980 Apr 3;302(14):765–769. doi: 10.1056/NEJM198004033021401. [DOI] [PubMed] [Google Scholar]
  9. Brodie M. J., Moore M. R., Thompson G. G., Goldbrrg A., Holti G. Haem biosynthesis in peripheral blood in erythropoietic protoporphyria. Clin Exp Dermatol. 1977 Dec;2(4):381–388. doi: 10.1111/j.1365-2230.1977.tb01579.x. [DOI] [PubMed] [Google Scholar]
  10. DeLeo V. A., Poh-Fitzpatrick M., Mathews-Roth M., Harber L. C. Erythropoietic protoporphyria. 10 years experience. Am J Med. 1976 Jan;60(1):8–22. doi: 10.1016/0002-9343(76)90528-3. [DOI] [PubMed] [Google Scholar]
  11. Grandchamp B., Phung N., Nordmann Y. Homozygous case of hereditary coproporphyria. Lancet. 1977 Dec 24;2(8052-8053):1348–1349. doi: 10.1016/s0140-6736(77)90386-5. [DOI] [PubMed] [Google Scholar]
  12. HAEGER-ARONSEN B. ERYTHROPOIETIC PROTOPORPHYRIA. A NEW TYPE OF INBORN ERROR OF METABOLISM. Am J Med. 1963 Oct;35:450–454. doi: 10.1016/0002-9343(63)90144-x. [DOI] [PubMed] [Google Scholar]
  13. Kassner R. J., Walchak H. Heme formation from Fe(II) and porphyrin in the absence of ferrochelatase activity. Biochim Biophys Acta. 1973 Apr 28;304(2):294–303. doi: 10.1016/0304-4165(73)90247-x. [DOI] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Lamon J. M., Poh-Fitzpatrick M. B., Lamola A. A. Hepatic protoporphyrin production in human protoporphyria. Effects of intravenous hematin and analysis of erythrocyte protoporphyrin distribution. Gastroenterology. 1980 Jul;79(1):115–125. [PubMed] [Google Scholar]
  16. Perlroth M. G., Tschudy D. P., Ratner A., Spaur W., Redeker A. The effect of diet in variegate (South African genetic) porphyria. Metabolism. 1968 Jul;17(7):571–581. doi: 10.1016/0026-0495(68)90015-2. [DOI] [PubMed] [Google Scholar]
  17. RUTH G. R., Schwartz S., Stephenson B. Bovine protoporphyria: the first nonhuman model of this hereditary photosensitizing disease. Science. 1977 Oct 14;198(4313):199–201. doi: 10.1126/science.905823. [DOI] [PubMed] [Google Scholar]
  18. Redeker A. G., Sterling R. E. The "glucose effect" in erythropoietic protoporphyria. Arch Intern Med. 1968 May;121(5):446–448. [PubMed] [Google Scholar]
  19. TSCHUDY D. P., WELLAND F. H., COLLINS A., HUNTER G., Jr THE EFFECT OF CARBOHYDRATE FEEDING ON THE INDUCTION OF DELTA-AMINOLEVULINIC ACID SYNTHETASE. Metabolism. 1964 May;13:396–406. doi: 10.1016/0026-0495(64)90113-1. [DOI] [PubMed] [Google Scholar]
  20. Watson C. J., Pierach C. A., Bossenmaier I., Cardinal R. Postulated deficiency of hepatic heme and repair by hematin infusions in the "inducible" hepatic porphyrias. Proc Natl Acad Sci U S A. 1977 May;74(5):2118–2120. doi: 10.1073/pnas.74.5.2118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. de Goeij A. F., Christianse K., van Steveninck J. Decreased haem synthetase activity in blood cells of patients with erythropoietic protoporphyria. Eur J Clin Invest. 1975 Sep 12;5(5):397–400. doi: 10.1111/j.1365-2362.1975.tb00470.x. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES