Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Hereditary coproporphyria

Ashwani K Singal, MD, MS
Karl E Anderson, MD, FACP
Section Editor
Stanley L Schrier, MD
Deputy Editor
Jennifer S Tirnauer, MD


Hereditary coproporphyria (HCP; OMIM #121300) is one of the acute hepatic porphyrias resulting in neurovisceral symptoms that are identical to those seen in acute intermittent porphyria (AIP) and variegate porphyria (VP) [1-3]. In contrast to AIP, blistering skin lesions, similar to those seen in VP and porphyria cutanea tarda (PCT), may also occur.

HCP is due to deficient activity of the mitochondrial enzyme coproporphyrinogen oxidase (CPOX), the sixth enzyme in the heme biosynthetic pathway (table 1 and figure 1) [4,5]. Affected individuals are heterozygous for mutations of the gene for that enzyme.

The clinical features, diagnosis, and treatment of HCP will be discussed here. A general review of the porphyrias is presented separately. (See "Porphyrias: An overview".)

The other acute porphyrias are also discussed separately. (See "Pathogenesis, clinical manifestations, and diagnosis of acute intermittent porphyria" and "Variegate porphyria" and "ALA dehydratase porphyria".)


HCP is the third most common acute porphyria after AIP and VP. The disease is mostly reported from Europe and North America, but is expected to occur in all ethnic groups. A prevalence of two per million was estimated in Denmark [6]. HCP typically manifests after puberty in heterozygotes, and more commonly in women. Homozygous cases of HCP and a genetic variant form termed harderoporphyria have been described, with disease onset in childhood [7-10].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Jun 16, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. BERGER H, GOLDBERG A. Hereditary coproporphyria. Br Med J 1955; 2:85.
  2. Brodie MJ, Thompson GG, Moore MR, et al. Hereditary coproporphyria. Demonstration of the abnormalities in haem biosynthesis in peripheral blood. Q J Med 1977; 46:229.
  3. Martásek P. Hereditary coproporphyria. Semin Liver Dis 1998; 18:25.
  4. Elder GH, Evans JO, Thomas N. The primary enzyme defect in hereditary coproporphyria. Lancet 1976; 2:1217.
  5. Martasek P, Camadro JM, Delfau-Larue MH, et al. Molecular cloning, sequencing, and functional expression of a cDNA encoding human coproporphyrinogen oxidase. Proc Natl Acad Sci U S A 1994; 91:3024.
  6. With TK. Hereditary coproporphyria and variegate porphyria in Denmark. Dan Med Bull 1983; 30:106.
  7. Martasek P, Nordmann Y, Grandchamp B. Homozygous hereditary coproporphyria caused by an arginine to tryptophane substitution in coproporphyrinogen oxidase and common intragenic polymorphisms. Hum Mol Genet 1994; 3:477.
  8. Grandchamp B, Phung N, Nordmann Y. Homozygous case of hereditary coproporphyria. Lancet 1977; 2:1348.
  9. Nordmann Y, Grandchamp B, de Verneuil H, et al. Harderoporphyria: a variant hereditary coproporphyria. J Clin Invest 1983; 72:1139.
  10. Lamoril J, Martasek P, Deybach JC, et al. A molecular defect in coproporphyrinogen oxidase gene causing harderoporphyria, a variant form of hereditary coproporphyria. Hum Mol Genet 1995; 4:275.
  11. Andant C, Puy H, Deybach JC, et al. Occurrence of hepatocellular carcinoma in a case of hereditary coproporphyria. Am J Gastroenterol 1997; 92:1389.
  12. Kühnel A, Gross U, Doss MO. Hereditary coproporphyria in Germany: clinical-biochemical studies in 53 patients. Clin Biochem 2000; 33:465.
  13. Barohn RJ, Sanchez JA, Anderson KE. Acute peripheral neuropathy due to hereditary coproporphyria. Muscle Nerve 1994; 17:793.
  14. Seshabhattar P, Morrow JS. Syndrome of inappropriate antidiuretic hormone secretion associated with coproporphyria: case report and review of literature. Endocr Pract 2007; 13:164.
  15. Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005; 142:439.
  16. Allen KR, Whatley SD, Degg TJ, Barth JH. Hereditary coproporphyria: comparison of molecular and biochemical investigations in a large family. J Inherit Metab Dis 2005; 28:779.
  17. Blake D, McManus J, Cronin V, Ratnaike S. Fecal coproporphyrin isomers in hereditary coproporphyria. Clin Chem 1992; 38:96.
  18. Sassa S. Modern diagnosis and management of the porphyrias. Br J Haematol 2006; 135:281.
  19. Brodie MJ, Moore MR, Thompson GG, et al. Pregnancy and the acute porphyrias. Br J Obstet Gynaecol 1977; 84:726.
  20. Elder GH, Evans JO. Evidence that the coproporphyrinogen oxidase activity of rat liver is situated in the intermembrane space of mitochondria. Biochem J 1978; 172:345.
  21. Grandchamp B, Phung N, Nordmann Y. The mitochondrial localization of coproporphyrinogen III oxidase. Biochem J 1978; 176:97.
  22. Yoshinaga T, Sano S. Coproporphyrinogen oxidase. I. Purification, properties, and activation by phospholipids. J Biol Chem 1980; 255:4722.
  23. Meissner P, Adams P, Kirsch R. Allosteric inhibition of human lymphoblast and purified porphobilinogen deaminase by protoporphyrinogen and coproporphyrinogen. A possible mechanism for the acute attack of variegate porphyria. J Clin Invest 1993; 91:1436.
  24. Elder GH, Smith SG, Smyth SJ. Laboratory investigation of the porphyrias. Ann Clin Biochem 1990; 27 ( Pt 5):395.
  25. Cacheux V, Martasek P, Fougerousse F, et al. Localization of the human coproporphyrinogen oxidase gene to chromosome band 3q12. Hum Genet 1994; 94:557.
  26. Fujita H, Kondo M, Taketani S, et al. Characterization and expression of cDNA encoding coproporphyrinogen oxidase from a patient with hereditary coproporphyria. Hum Mol Genet 1994; 3:1807.
  27. Lamoril J, Puy H, Whatley SD, et al. Characterization of mutations in the CPO gene in British patients demonstrates absence of genotype-phenotype correlation and identifies relationship between hereditary coproporphyria and harderoporphyria. Am J Hum Genet 2001; 68:1130.
  28. Gross U, Puy H, Meissauer U, et al. A molecular, enzymatic and clinical study in a family with hereditary coproporphyria. J Inherit Metab Dis 2002; 25:279.
  29. To-Figueras J, Badenas C, Enríquez MT, et al. Biochemical and genetic characterization of four cases of hereditary coproporphyria in Spain. Mol Genet Metab 2005; 85:160.
  30. Sassa S, Kondo M, Taketani S, et al. Molecular defects of the coproporphyrinogen oxidase gene in hereditary coproporphyria. Cell Mol Biol (Noisy-le-grand) 1997; 43:59.
  31. Akagi R, Inoue R, Muranaka S, et al. Dual gene defects involving delta-aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient. Br J Haematol 2006; 132:237.
  32. Jackson AH, Jones DM, Philip G, et al. Synthetic and biosynthetic studies of porphyrins, Part IV. Further studies of the conversion of corporporhyrinogen-III to protoporphyrin-IX: mass spectrometric investigations of the incubation of specifically deuteriated coproporhyringen-III with chicken red cell haemolysates. Int J Biochem 1980; 12:681.
  33. Lamoril J, Puy H, Gouya L, et al. Neonatal hemolytic anemia due to inherited harderoporphyria: clinical characteristics and molecular basis. Blood 1998; 91:1453.
  34. Hasanoglu A, Balwani M, Kasapkara CS, et al. Harderoporphyria due to homozygosity for coproporphyrinogen oxidase missense mutation H327R. J Inherit Metab Dis 2011; 34:225.
  35. Deacon AC, Peters TJ. Identification of acute porphyria: evaluation of a commercial screening test for urinary porphobilinogen. Ann Clin Biochem 1998; 35 ( Pt 6):726.
  36. Harper P, Wahlin S. Treatment options in acute porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria. Curr Treat Options Gastroenterol 2007; 10:444.
  37. Hunter JA, Khan SA, Hope E, et al. Hereditary coproporphyria. Photosensitivity, jaundice and neuropsychiatric manifestations associated with pregnancy. Br J Dermatol 1971; 84:301.
  38. Meissner PN, Harrison GG, Hift RJ. Propofol as an i.v. anaesthetic induction agent in variegate porphyria. Br J Anaesth 1991; 66:60.
  39. Anderson KE, Spitz IM, Sassa S, et al. Prevention of cyclical attacks of acute intermittent porphyria with a long-acting agonist of luteinizing hormone-releasing hormone. N Engl J Med 1984; 311:643.