Erythropoietic protoporphyria in Sweden: Demographic, clinical, biochemical and genetic characteristics

Journal of Internal Medicine

Volumn 269, Issue 3, 2011, Pages 278-288

  Wahlin, S ^a   Floderus, Y ^b   Stal P ^a   Harper, P ^b  

^a Departments of Gastroenterology and Hepatology   (Sweden)

^b KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Anaemia; Clinical features; Erythropoietic protoporphyria; Iron deficiency; Mutations; Vitamin D

Indexed keywords

BETA CAROTENE; ERYTHROCYTE PROTOPORPHYRIN; FERRITIN; FERROCHELATASE; IRON; TRANSFERRIN; VITAMIN D;

ADOLESCENT; ADULT; AGED; ARTICLE; CHEMICAL ANALYSIS; CHILD; COLD STRESS; CONTROLLED STUDY; DELAYED DIAGNOSIS; DEMOGRAPHY; ERYTHROPOIESIS; ERYTHROPOIETIC PROTOPORPHYRIA; EXERCISE; FEMALE; FERRITIN BLOOD LEVEL; GENE MUTATION; GENETIC TRAIT; GENOTYPE; HEAT; HUMAN; IRON METABOLISM; LIGHT; MAJOR CLINICAL STUDY; MALE; MOLECULAR DIAGNOSIS; PHENOTYPE; PHOTOSENSITIVITY; PORPHYRIN METABOLISM; PRESCHOOL CHILD; PREVALENCE; PRIORITY JOURNAL; QUALITY OF LIFE; QUESTIONNAIRE; RECOMMENDED DRUG DOSE; SCHOOL CHILD; SEX DIFFERENCE; SKIN MANIFESTATION; SUNLIGHT; SWEDEN; TRANSFERRIN BLOOD LEVEL; VITAMIN BLOOD LEVEL; VITAMIN D METABOLISM; WIND;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; BETA CAROTENE; CHILD; CROSS-SECTIONAL STUDIES; ERYTHROPOIESIS; FEMALE; FERROCHELATASE; GENOTYPE; HUMANS; MALE; MIDDLE AGED; MUTATION; PHOTOSENSITIVITY DISORDERS; PORPHYRINS; PROTOPORPHYRIA, ERYTHROPOIETIC; SWEDEN; VITAMIN D; YOUNG ADULT;

EID: 79951699208     PISSN: 09546820     EISSN: 13652796     Source Type: Journal    
DOI: 10.1111/j.1365-2796.2010.02236.x     Document Type: Article

References (45)

1. Bloomer JR, Wang Y, Singhal A, Risheg H. Biochemical abnormality in erythropoietic protoporphyria: Cause and consequences. J Pediatr Gastroenterol Nutr 2006; 43(Suppl. 1): S36-40.
2. Went LN, Klasen EC. Genetic aspects of erythropoietic protoporphyria. Ann Hum Genet 1984; 48 (Pt 2): 105-17.
3. 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: 574-81.
4. Parker M, Corrigall AV, Hift RJ, Meissner PN. Molecular characterization of erythropoietic protoporphyria in South Africa. Br J Dermatol 2008; 159: 182-91.
5. Haeger-Aronsen B, Krook G. Erythropoietic protoporphyria. A study of known cases in Sweden. Acta Med Scand Suppl 1966; 445: 48-55.
6. Wiman A, Floderus Y, Harper P. Novel mutations and phenotypic effect of the splice site modulator IVS3-48C in nine Swedish families with erythropoietic protoporphyria. J Hum Genet 2003; 48: 70-6.
7. Sassa S. Modern diagnosis and management of the porphyrias. Br J Haematol 2006; 135: 281-92.
8. 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: 174-9.
9. Mathews-Roth MM. Treatment of the cutaneous porphyrias. Clin Dermatol 1998; 16: 295-8.
10. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266-81.
11. NORIP. Nordic Reference Interval Project. Available at: (accessed on 30 March 2010).
12. The Human Gene Mutation Database (HGMD). Available at: (accessed on 30 March 2010).
13. Whatley SD, Ducamp S, Gouya L et al. C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. Am J Hum Genet 2008; 83: 408-14.
14. Wahlin S, Srikanthan N, Hamre B, Harper P, Brun A. Protection from phototoxic injury during surgery and endoscopy in erythropoietic protoporphyria. Liver Transpl 2008; 14: 1340-6.
15. Poh-Fitzpatrick MB. Human protoporphyria: reduced cutaneous photosensitivity and lower erythrocyte porphyrin levels during pregnancy. J Am Acad Dermatol 1997; 36: 40-3.
16. 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.
17. Minder EI, Schneider-Yin X, Steurer J, Bachmann LM. A systematic review of treatment options for dermal photosensitivity in erythropoietic protoporphyria. Cell Mol Biol (Noisy-le-grand) 2009; 55: 84-97.
18. Moseley H, Cameron H, MacLeod T, Clark C, Dawe R, Ferguson J. New sunscreens confer improved protection for photosensitive patients in the blue light region. Br J Dermatol 2001; 145: 789-94.
19. Rufener EA. Erythropoietic protoporphyria: a study of its psychosocial aspects. Br J Dermatol 1987; 116: 703-8.
20. Spelt JMC, de Rooij FWM, Wilson JHP, Zandbergen AAM. Vitamin D deficiency in patients with erythropoietic protoporphyria. J Inherit Metab Dis 2009. DOI.
21. Holme SA, Anstey AV, Badminton MN, Elder GH. Serum 25-hydroxyvitamin D in erythropoietic protoporphyria. Br J Dermatol 2008; 159: 211-3.
22. Holme SA, Worwood M, Anstey AV, Elder GH, Badminton MN. Erythropoiesis and iron metabolism in dominant erythropoietic protoporphyria. Blood 2007; 110: 4108-10.
23. Delaby C, Lyoumi S, Ducamp S et al. Excessive erythrocyte ppix influences the hematologic status and iron metabolism in patients with dominant erythropoietic protoporphyria. Cell Mol Biol (Noisy-le-grand) 2009; 55: 45-52.
24. Snellman G, Melhus H, Gedeborg R et al. Seasonal genetic influence on serum 25-hydroxyvitamin D levels: a twin study. PLoS ONE 2009; 4: e7747.
25. Landin-Wilhelmsen K, Wilhelmsen L, Wilske J et al. Sunlight increases serum 25(OH) vitamin D concentration whereas 1, 25(OH)2D3 is unaffected. Results from a general population study in Goteborg, Sweden (The WHO MONICA Project). Eur J Clin Nutr 1995; 49: 400-7.
26. Parkes J, Harris S, Lightstone E, Chambers J, Kooner J, Roderick P. Raised ALT is associated with ethnicity in a large general population cohort in UK (LOLIPOP Study). Hepatology 2009; 50: 777A.
27. Dazzani F, Giacomoni P, Foschi FG et al. Prevalence of transaminase abnormalities in general population in XXI century: preliminary results from the Bagnacavallo study. Hepatology 2009; 50: 794A.
28. Harper P, Wahlin S. Treatment options in acute porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria. Curr Treat Options Gastroenterol 2007; 10: 444-55.
29. Turnbull A, Baker H, Vernon-Roberts B, Magnus IA. Iron metabolism in porphyria cutanea tarda and in erythropoietic protoporphyria. Q J Med 1973; 42: 341-55.
30. Baker H. Erythropoietic protoporphyria provoked by iron therapy. Proc R Soc Med 1971; 64: 610-1.
31. Milligan A, Graham-Brown RA, Sarkany I, Baker H. Erythropoietic protoporphyria exacerbated by oral iron therapy. Br J Dermatol 1988; 119: 63-6.
32. 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.
33. 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: 1070-2.
34. Gouya L, Martin-Schmitt C, Robreau AM et al. Contribution of a common single-nucleotide polymorphism to the genetic predisposition for erythropoietic protoporphyria. Am J Hum Genet 2006; 78: 2-14.
35. Whatley SD, Mason NG, Khan M et al. Autosomal recessive erythropoietic protoporphyria in the United Kingdom: prevalence and relationship to liver disease. J Med Genet 2004; 41: e105.
36. Aplin C, Whatley SD, Thompson P et al. Late-onset erythropoietic porphyria caused by a chromosome 18q deletion in erythroid cells. J Invest Dermatol 2001; 117: 1647-9.
37. Goodwin RG, Kell WJ, Laidler P et al. Photosensitivity and acute liver injury in myeloproliferative disorder secondary to late-onset protoporphyria caused by deletion of a ferrochelatase gene in hematopoietic cells. Blood 2006; 107: 60-2.
38. Sassa S, Akagi R, Nishitani C, Harigae H, Furuyama K. Late-onset porphyrias: what are they? Cell Mol Biol (Noisy-le-grand) 2002; 48: 97-101.
39. 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: 2790-4.
40. Harms J, Lautenschlager S, Minder CE, Minder EI. An alpha-melanocyte-stimulating hormone analogue in erythropoietic protoporphyria. N Engl J Med 2009; 360: 306-7.
41. Wahlin S, Harper P. The role for BMT in erythropoietic protoporphyria. Bone Marrow Transpl 2010; 45: 393-4.
42. Henriksson M, Timonen K, Mustajoki P et al. Four novel mutations in the ferrochelatase gene among erythropoietic protoporphyria patients. J Invest Dermatol 1996; 106: 346-50.
43. Di Pierro E, Moriondo V, Cappellini MD. Human gene mutations. Gene symbol: FECH. Disease: porphyria, erythropoietic. Hum Genet 2004; 114: 221.
44. Rufenacht UB, Gouya L, Schneider-Yin X et al. Systematic analysis of molecular defects in the ferrochelatase gene from patients with erythropoietic protoporphyria. Am J Hum Genet 1998; 62: 1341-52.
45. Di Pierro E, Brancaleoni V, Besana V, Ausenda S, Drury S, Cappellini MD. A 10376bp deletion of FECH gene responsible for erythropoietic protoporphyria. Blood Cells Mol Dis 2008; 40: 233-6.