Which of the following best describes the inheritance pattern illustrated in figure 1 protoporphyria

1. Magnus IA, Jarrett A, Prankerd TA, Rimington C. Erythropoietic protoporphyria. A new porphyria syndrome with solar urticaria due to protoporphyrinaemia. Lancet. 1961;2:448–451. [PubMed] [Google Scholar]

2. Bonkovsky HL, Bloomer JR, Ebert PS, Mahoney MJ. Heme synthetase deficiency in human protoporphyria. Demonstration of the defect in liver and cultured skin fibroblasts. J Clin Invest. 1975;56:1139–1148. [PMC free article] [PubMed] [Google Scholar]

3. Taketani S, Inazawa J, Nakahashi Y, Abe T, Tokunaga R. Structure of the human ferrochelatase gene. Exon/intron gene organization and location of the gene to chromosome 18. EurJ Biochem. 1992;205:217–222. [PubMed] [Google Scholar]

4. Whitcombe DM, Carter NP, Albertson DG, Smith SJ, Rhodes DA, Cox TM. Assignment of the human ferrochelatase gene (FECH) and a locus for protoporphyria to chromosome 18q22. Genomics. 1991;11:1152–1154. [PubMed] [Google Scholar]

5. Sarkany RP, Alexander GJ, Cox TM. Recessive inheritance of erythropoietic protoporphyria with liver failure. Lancet. 1994;343:1394–1396. [PubMed] [Google Scholar]

6. Gouya L, Martin-Schmitt C, Robreau AM, Austerlitz F, Da Silva V, et al. Contribution of a common single-nucleotide polymorphism to the genetic predisposition for erythropoietic protoporphyria. Am J Hum Genet. 2006;78:2–14. [PMC free article] [PubMed] [Google Scholar]

7. Gouya L, Puy H, Robreau AM, Bourgeois M, Lamoril J, et al. The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH. Nat Genet. 2002;30:27–28. [PubMed] [Google Scholar]

8. Whatley SD, Mason NG, Holme SA, Anstey AV, Elder GH, Badminton MN. Gene dosage analysis identifies large deletions of the FECH gene in 10% of families with erythropoietic protoporphyria. J Invest Dermatol. 2007;127:2790–2794. [PubMed] [Google Scholar]

9. Straka JG, Hill HD, Krikava JM, Kools AM, Bloomer JR. Immunochemical studies of ferrochelatase protein: characterization of the normal and mutant protein in bovine and human protoporphyria. Am J Hum Genet. 1991;48:72–78. [PMC free article] [PubMed] [Google Scholar]

10. Rufenacht UB, Gouya L, Schneider-Yin X, Puy H, Schäfer BW, et al. Systematic analysis of molecular defects in the ferrochelatase gene from patients with erythropoietic protoporphyria. Am J Hum Genet. 1998;62:1341–1352. [PMC free article] [PubMed] [Google Scholar]

11. Bloomer JR, Hill HD, Kools AM, Straka JG. Heme synthesis in protoporphyria. Curr Probl Dermatol. 1991;20:135–147. [PubMed] [Google Scholar]

12. Samuel D, Boboc B, Bernuau J, Bismuth H, Benhamou JP. Liver transplantation for protoporphyria. Evidence for the predominant role of the erythropoietic tissue in protoporphyrin overproduction. Gastroenterology. 1988;95:816–819. [PubMed] [Google Scholar]

13. Schmidt H, Snitker G, Thomsen K, Lintrup J. Erythropoietic protoporphyria. A clinical study based on 29 cases in 14 families. Arch Dermatol. 1974;110:58–64. [PubMed] [Google Scholar]

14. DeLeo VA, Poh-Fitzpatrick M, Mathews-Roth M, Harber LC. Erythropoietic protoporphyria. 10 years experience. Am J Med. 1976;60:8–22. [PubMed] [Google Scholar]

15. Baart de la Faille H, Bijlmer-Iest JC, van Hattum J, Koningsberger J, Rade-makers LH, van Weelden H. Erythropoietic protoporphyria: clinical aspects with emphasis on the skin. Curr Probl Dermatol. 1991;20:123–134. [PubMed] [Google Scholar]

16. Holme SA, Anstey AV, Finlay AY, Elder GH, Badminton MN. Erythropoietic protoporphyria in the U.K.: clinical features and effect on quality of life. Br J Dermatol. 2006;155:574–581. [PubMed] [Google Scholar]

17. Chen FP, Risheg H, Liu Y, Bloomer J. Ferrochelatase gene mutations in erythropoietic protoporphyria: focus on liver disease. Cell Mol Biol (Noisy-le-grand) 2002;48:83–89. [PubMed] [Google Scholar]

18. Poh-Fitzpatrick MB. The erythropoietic porphyrias. Dermatol Clin. 1986;4:291–296. [PubMed] [Google Scholar]

19. Reisenauer AK, Soon SL, Lee KK, Hanifin JM. Erythropoietic protoporphyria presenting with liver failure in adulthood. Dermatology. 2005;210:72–73. [PubMed] [Google Scholar]

20. Lee RG, Avner DL, Berenson MM. Structure-function relationships of protoporphyrin-induced liver injury. Arch Pathol Lab Med. 1984;108:744–746. [PubMed] [Google Scholar]

21. Cox TM, Alexander GJ, Sarkany RP. Protoporphyria. Semin Liver Dis. 1998;18:85–93. [PubMed] [Google Scholar]

22. Todd DJ. Gallstones in children. Am J Dis Child. 1991;145:971–972. [PubMed] [Google Scholar]

23. Rank JM, Carithers R, Bloomer J. Evidence for neurological dysfunction in end-stage protoporphyric liver disease. Hepatology. 1993;18:1404–1409. [PubMed] [Google Scholar]

24. Muley SA, Midani HA, Rank JM, Carithers R, Parry GJ. Neuropathy in erythropoietic protoporphyrias. Neurology. 1998;51:262–265. [PubMed] [Google Scholar]

25. Lock G, Holstege A, Mueller AR, Christe W, Doss MO, et al. Liver failure in erythropoietic protoporphyria associated with choledocholithiasis and severe posttransplantation polyneuropathy. Liver. 1996;16:211–217. [PubMed] [Google Scholar]

26. Nguyen L, Blust M, Bailin M, Melendez L, Raines DE. Photosensitivity and perioperative polyneuropathy complicating orthotopic liver transplantation in a patient with erythropoietic protoporphyria. Anesthesiology. 1999;91:1173–1175. [PubMed] [Google Scholar]

27. Bonkovsky HL, Thapar M. Porphyria. In: Rakel RE, Bope ET, editors. Conn's Current Therapy. Philadelphia, PA: Elsevier Health; 2008. pp. 469–474. [Google Scholar]

28. Lamola AA, Piomelli S, Poh-Fitzpatrick MG, Yamane T, Harber LC. Erythropoietic protoporphyria and lead intoxication: the molecular basis for difference in cutaneous photosensitivity. II. Different binding of erythrocyte protoporphyrin to hemoglobin. J Clin Invest. 1975;56:1528–1535. [PMC free article] [PubMed] [Google Scholar]

29. Poh-Fitzpatrick MB. Protoporphyrin metabolic balance in human protoporphyria. Gastroenterology. 1985;88:1239–1242. [PubMed] [Google Scholar]

30. Bloomer JR. The liver in protoporphyria. Hepatology. 1988;8:402–407. [PubMed] [Google Scholar]

31. Gross U, Frank M, Doss MO. Hepatic complications of erythropoietic protoporphyria. Photodermatol Photoimmunol Photomed. 1998;14:52–57. [PubMed] [Google Scholar]

32. MacDonald DM, Germain D, Perrot H. The histopathology and ultrastructure of liver disease in erythropoietic protoporphyria. Br J Dermatol. 1981;104:7–17. [PubMed] [Google Scholar]

33. Mathews-Roth MM, Pathak MA, Fitzpatrick TB, Harber LH, Kass EH. Beta carotene therapy for erythropoietic protoporphyria and other photosensitivity diseases. Arch Dermatol. 1977;113:1229–1232. [PubMed] [Google Scholar]

34. Mathews-Roth MM, Rosner B. Long-term treatment of erythropoietic protoporphyria with cysteine. Photodermatol Photoimmunol Photomed. 2002;18:307–309. [PubMed] [Google Scholar]

35. McCullough AJ, Barron D, Mullen KD, Petrelli M, Park MC, et al. Fecal protoporphyrin excretion in erythropoietic protoporphyria: effect of cholestyramine and bile acid feeding. Gastroenterology. 1988;94:177–181. [PubMed] [Google Scholar]

36. Bloomer JR. Pathogenesis and therapy of liver disease in protoporphyria. Yale J Biol Med. 1979;52:39–48. [PMC free article] [PubMed] [Google Scholar]

37. Gorchein A, Foster GR. Liver failure in protoporphyria: long-term treatment with oral charcoal. Hepatology. 1999;29:995–996. [PubMed] [Google Scholar]

38. Komatsu H, Ishii K, Imamura K, Maruyama K, Yonei Y, et al. A case of erythropoietic protoporphyria with liver cirrhosis suggesting a therapeutic value of supplementation with alpha-tocopherol. Hepatol Res. 2000;18:298–309. [PubMed] [Google Scholar]

39. Pirlich M, Lochs H, Schmidt HH. Liver cirrhosis in erythropoietic protoporphyria: improvement of liver function with ursodeoxycholic acid. Am J Gastroenterol. 2001;96:3468–3469. [PubMed] [Google Scholar]

40. Rademakers LH, Cleton MI, Kooijman C, Baart de la Faille H, van Hattum J. Early involvement of hepatic parenchymal cells in erythrohepatic protoporphyria? An ultrastructural study of patients with and without overt liver disease and the effect of chenodeoxycholic acid treatment. Hepatology. 1990;11:449–457. [PubMed] [Google Scholar]

41. Van Hattum J, Baart de la Faille H, Van den Berg JW, Edixhoven-Bosdijk A, Wilson JH. Chenodeoxycholic acid therapy in erythrohepatic protoporphyria. J Hepatol. 1986;3:407–412. [PubMed] [Google Scholar]

42. Abitbol M, Puy H, Sabaté JM, Guénet JL, Deybach JC, Montagutelli X. Ursodesoxycholic acid and heme-arginate are unable to improve hematopoiesis and liver injury in an erythropoietic protoporphyria mouse model. Physiol Res. 2006;55(suppl 2):S93–S101. [PubMed] [Google Scholar]

43. Holme SA, Worwood M, Anstey AV, Elder GH, Badminton MN. Erythropoiesis and iron metabolism in dominant erythropoietic protoporphyria. Blood. 2007;110:4108–4110. [PubMed] [Google Scholar]

44. Holme SA, Thomas CL, Whatley SD, Bentley DP, Anstey AV, Badminton MN. Symptomatic response of erythropoietic protoporphyria to iron supplementation. J Am Acad Dermatol. 2007;56:1070–1072. [PubMed] [Google Scholar]

45. Gordeuk VR, Brittenham GM, Hawkins CW, Mukhtar H, Bickers DR. Iron therapy for hepatic dysfunction in erythropoietic protoporphyria. Ann Intern Med. 1986;105:27–31. [PubMed] [Google Scholar]

46. Milligan A, Graham-Brown RA, Sarkany I, Baker H. Erythropoietic protoporphyria exacerbated by oral iron therapy. Br J Dermatol. 1988;119:63–66. [PubMed] [Google Scholar]

47. McClements BM, Bingham A, Callender ME, Trimble ER. Erythropoietic protoporphyria and iron therapy. Br J Dermatol. 1990;122:423–424. [PubMed] [Google Scholar]

48. van Wijk HJ, van Hattum J, Baart de la Faille H, van den Berg JW, Edixhoven-Bosdijk A, Wilson JH. Blood exchange and transfusion therapy for acute cholestasis in protoporphyria. Dig Dis Sci. 1988;33:1621–1625. [PubMed] [Google Scholar]

49. Bloomer JR, Pierach CA. Effect of hematin administration to patients with protoporphyria and liver disease. Hepatology. 1982;2:817–821. [PubMed] [Google Scholar]

50. Todd DJ, Callender ME, Mayne EE, Walsh M, Burrows D. Erythropoietic protoporphyria, transfusion therapy and liver disease. Br J Dermatol. 1992;127:534–537. [PubMed] [Google Scholar]

51. Lamon JM, Poh-Fitzpatrick MB, Lamola AA. Hepatic protoporphyrin production in human protoporphyria. Effects of intravenous hematin and analysis of erythrocyte protoporphyrin distribution. Gastroenterology. 1980;79:115–125. [PubMed] [Google Scholar]

52. Reichheld JH, Katz E, Banner BF, Szymanski IO, Saltzman JR, Bonkovsky HL. The value of intravenous heme-albumin and plasmapheresis in reducing postoperative complications of orthotopic liver transplantation for erythropoietic protoporphyria. Transplantation. 1999;67:922–928. [PubMed] [Google Scholar]

53. Dellon ES, Szczepiorkowski ZM, Dzik WH, Graeme-Cook F, Ades A, et al. Treatment of recurrent allograft dysfunction with intravenous hematin after liver transplantation for erythropoietic protoporphyria. Transplantation. 2002;73:911–915. [PubMed] [Google Scholar]

54. Do KD, Banner BF, Katz E, Szymanski IO, Bonkovsky HL. Benefits of chronic plasmapheresis and intravenous heme-albumin in erythropoietic protoporphyria after orthotopic liver transplantation. Transplantation. 2002;73:469–472. [PubMed] [Google Scholar]

55. Eefsen M, Rasmussen A, Wulf HC, Brock A, Hansen BA. Erythropoietic protoporphyria and pretransplantation treatment with nonbiological liver assist devices. Liver Transpl. 2007;13:655–657. [PubMed] [Google Scholar]

56. McGuire BM, Bonkovsky HL, Carithers RL, Jr, Chung RT, Goldstein LI, et al. Liver transplantation for erythropoietic protoporphyria liver disease. Liver Transpl. 2005;11:1590–1596. [PubMed] [Google Scholar]

57. Poh-Fitzpatrick MB, Wang X, Anderson KE, Bloomer JR, Bolwell B, Lichtin AE. Erythropoietic protoporphyria: altered phenotype after bone marrow transplantation for myelogenous leukemia in a patient heteroallelic for ferrochelatase gene mutations. J Am Acad Dermatol. 2002;46:861–866. [PubMed] [Google Scholar]

58. Seth AK, Badminton MN, Mirza D, Russell S, Elias E. Liver transplantation for porphyria: who, when, and how? Liver Transpl. 2007;13:1219–1227. [PubMed] [Google Scholar]

59. Wahlin S, Aschan J, Bjornstedt M, Broome U, Harper P. Curative bone marrow transplantation in erythropoietic protoporphyria after reversal of severe cholestasis. J Hepatol. 2007;46:174–179. [PubMed] [Google Scholar]

60. Rand EB, Bunin N, Cochran W, Ruchelli E, Olthoff KM, Bloomer JR. Sequential liver and bone marrow transplantation for treatment of erythropoietic protoporphyria. Pediatrics. 2006;118:e1896–e1899. [PubMed] [Google Scholar]

61. Bonkovsky HL, Schned AR. Fatal liver failure in protoporphyria. Synergism between ethanol excess and the genetic defect. Gastroenterology. 1986;90:191–201. [PubMed] [Google Scholar]

62. Mathews-Roth MM. The consequences of not diagnosing erythropoietic protoporphyria. Arch Dermatol. 1980;116:407. [PubMed] [Google Scholar]


Page 2

Classification and Major Features of Human Porphyrias

Clinical features
DiseasePrimary enzymatic defectAutosomal inheritanceNeurovisceral symptomsPhotosensitivity dermatosis
Acute/inducible pofphyiias
ALA-D deficiency porphyriaALA dehydrataseRecessive+--
Acute intermittent porphyriaPBG deaminaseDominant+--
Hereditary coproporphyriaCoproporphyrinogen oxidaseDominant++
Variegate porphyriaProtoporphyrinogen oxidaseDominant++
Chronic cutaneous porphyrias
Congenital erythropoieticUroporphyrinogen III cosynthaseRecessive--++
Hepatoerythropoietic porphyriaUroporphyrinogen decarboxylaseRecessive+/-+
Porphyria cutanea tardaUroporphyrinogen decarboxylaseDominant (acquired variant exists)--+
ProtoporphyriaFerrochelataseDominant†--*+