Porphyrias and photosensitivity: pathophysiology for the clinician

References

• Ades IZ. Heme production in animal tissues: the regulation of biogenesis of δ-aminolevulinate synthase. Int J Biochem. 1990;22:565–578.
   PubMedGoogle Scholar
• Layer G, Reichelt J, Jahn D, et al. Structure and function of enzymes in heme biosynthesis. Protein Sci. 2010;19:1137–1161.
   PubMed Web of Science ®Google Scholar
• Sassa S. The porphyrias. Photodermatol Photoimmunol Photomed. 2002;18:56–67.
   PubMed Web of Science ®Google Scholar
• Correia MA, Sinclair PR, De Matteis F. Cytochrome P450 regulation: the interplay between its heme and apoprotein moieties in synthesis, assembly, repair, and disposal. Drug Metab Rev. 2011;43:1–26.
   PubMed Web of Science ®Google Scholar
• Ponka P. Cell Biology of Heme. Am J Med Sci. 1999;318:241–256.
   PubMed Web of Science ®Google Scholar
• Minder EI, Barman-Aksözen J. Iron and erythropoietic porphyrias. Blood. 2015;126:130–132.
   PubMed Web of Science ®Google Scholar
• Balwani M, Desnick RJ. The porphyrias: advances in diagnosis and treatment. Blood. 2012;120:4496–4504.
   PubMed Web of Science ®Google Scholar
• Bonkovsky HL, Maddukuri VC, Yazici C, et al. Acute porphyrias in the USA: features of 108 subjects from porphyrias consortium. Am J Med. 2014;127:1233–1241.
   PubMed Web of Science ®Google Scholar
• Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. N Engl J Med. 2017;377:862–872.
   PubMed Web of Science ®Google Scholar
• Brun S. Mechanisms of photosensitivity in porphyric patients with special emphasis onerythropoietic protoporphyria. J Photochem Photobiol B. 1991;10:285–302.
   PubMed Web of Science ®Google Scholar
• Besur S, Hou W, Schmeltzer P, et al. Clinically important features of porphyrin and heme metabolism and the porphyrias. Metabolites. 2014;4:977–1006.
   PubMedGoogle Scholar
• Liu LU, Phillips J, Bonkovsky H. Porphyrias Consortium of the Rare Diseases Clinical Research Network PC of the RDCR. Hepatoerythropoietic Porphyria. Seattle: University of Washington; 1993.
   Google Scholar
• Murphy GM. Diagnosis and management of the erythropoietic porphyrias. Dermatol Ther. 2003;16:57–64.
   PubMedGoogle Scholar
• 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;83:408–414.
   PubMed Web of Science ®Google Scholar
• Dawe R. An overview of the cutaneous porphyrias. F1000Research. 2017;6:1906.
   PubMedGoogle Scholar
• Gouya L, Martin-Schmitt C, Robreau AM, et al. Contribution of a common single-nucleotide polymorphism to the genetic predisposition for erythropoietic protoporphyria. The American Journal of Human Genetics. 2006 Jan 1;78(1):2–14.
   Google Scholar
• Crooks DR, Ghosh MC, Haller RG, et al. Posttranslational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery. Blood. 2010;115:860–869.
   PubMed Web of Science ®Google Scholar
• Barman-Aksoezen J, Girelli D, Aurizi C, et al. Disturbed iron metabolism in erythropoietic protoporphyria and association of GDF15 and gender with disease severity. J Inherit Metab Dis. 2017;40:433–441.
   PubMed Web of Science ®Google Scholar
• Labbé RF, Vreman HJ, Stevenson DK. Zinc protoporphyrin: a metabolite with a mission. Clin Chem. 1999;45:2060–2072.
   PubMed Web of Science ®Google Scholar
• Chung J, Wittig JG, Ghamari A, et al. Erythropoietin signaling regulates heme biosynthesis. Elife. 2017;6.
   Web of Science ®Google Scholar
• Egan DN, Yang Z, Phillips J, et al. Inducing iron deficiency improves erythropoiesis and photosensitivity in congenital erythropoietic porphyria. Blood. 2015;126:257–261.
   PubMed Web of Science ®Google Scholar
• Elder G, Harper P, Badminton M, et al. The incidence of inherited porphyrias in Europe. J Inherit Metab Dis. 2013;36:849–857.
   PubMed Web of Science ®Google Scholar
• Badminton MN, Elder GH. Molecular mechanisms of dominant expression in porphyria. J Inherit Metab Dis. 2005;28:277–286.
   PubMed Web of Science ®Google Scholar
• Chen B, Solis-Villa C, Hakenberg J, et al. Acute Intermittent Porphyria: predicted Pathogenicity of HMBS Variants Indicates Extremely Low Penetrance of the Autosomal Dominant Disease. Hum Mutat. 2016;37:1215–1222.
   PubMed Web of Science ®Google Scholar
• Herrick AL, McColl KEL. Acute intermittent porphyria. Best Pract Res Clin Gastroenterol. 2005;19:235–249.
   PubMed Web of Science ®Google Scholar
• Enna SJ, Th K, Mccarson E The Role of GABA in the Mediation and Perception of Pain.
   Google Scholar
• Lindberg RLP, Martini R, Baumgartner M, et al. Motor neuropathy in porphobilinogen deaminase–deficient mice imitates the peripheral neuropathy of human acute porphyria. J Clin Invest. 1999;103:1127–1134.
   PubMed Web of Science ®Google Scholar
• Kuo H-C, Huang -C-C, Chu -C-C, et al. Neurological Complications of Acute Intermittent Porphyria. Eur Neurol. 2011;66:247–252.
   PubMed Web of Science ®Google Scholar
• Sardh E, Andersson DEH, Henrichson A, et al. Porphyrin precursors and porphyrins in three patients with acute intermittent porphyria and end-stage renal disease under different therapy regimes. Cell Mol Biol (Noisy-Le-Grand). 2009;55:66–71.
   PubMed Web of Science ®Google Scholar
• Ramanujam V-MS, Anderson KE. Porphyria Diagnostics-Part 1: a Brief Overview of the Porphyrias. Curr Protoc Hum Genet. 2015;86:17.20.1–26.
   PubMedGoogle Scholar
• Pischik E, Kauppinen R. An update of clinical management of acute intermittent porphyria. Appl Clin Genet. 2015;8:201–214.
   PubMedGoogle Scholar
• Schmitt C, Lenglet H, Yu A, et al. Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver. J Intern Med. 2018;284:78–91.
   PubMed Web of Science ®Google Scholar
• Stein P, Badminton M, Barth J, et al. Best practice guidelines on clinical management of acute attacks of porphyria and their complications. Ann Clin Biochem. 2013;50:217–223.
   PubMed Web of Science ®Google Scholar
• Sood G, Anderson K. Acute intermittent porphyria. BMJ Best Pract. 2018;1–28.
   Google Scholar
• Stein PE, Badminton MN, Rees DC. Update review of the acute porphyrias. Br J Haematol. 2017;176:527–538.
   PubMed Web of Science ®Google Scholar
• D’Avola D, Gonzalez Aseguinolaza G. Prospect and progress of gene therapy in acute intermittent porphyria. Expert Opin Orphan Drugs. 2016;4:711–717.
   Web of Science ®Google Scholar
• Bulaj ZJ, Phillips JD, Ajioka RS, et al. Hemochromatosis genes and other factors contributing to the pathogenesis of porphyria cutanea tarda. Blood. 2000;95:1565–1571.
   PubMed Web of Science ®Google Scholar
• Cantatore-Francis JL, Cohen-Pfeffer J, Balwani M, et al. Hepatoerythropoietic Porphyria Misdiagnosed as Child Abuse. Arch Dermatol. 2010;146:529–533.
   PubMedGoogle Scholar
• Horner ME, Alikhan A, Tintle S, et al. Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology. Int J Dermatol. 2013;52:1464–1480.
   PubMed Web of Science ®Google Scholar
• Elder GH, Roberts AG, de Salamanca RE. Genetics and pathogenesis of human uroporphyrinogen decarboxylase defects. Clin Biochem. 1989;22:163–168.
   PubMed Web of Science ®Google Scholar
• Ergen EN, Seidler E, Parekh S, et al. Is non-alcoholic steatohepatitis a predisposing factor to porphyria cutanea tarda? Photodermatol Photoimmunol Photomed. 2013;29:106–108.
   PubMed Web of Science ®Google Scholar
• Elder G, De Salamanca R, Urquhart A, et al. Immunoreactive uroporphyrinogen decarboxylase in the liver in porphyria cutanea tarda. The Lancet. 1985 Aug 3;326(8449):229–233.
   Google Scholar
• Phillips JD, Bergonia HA, Reilly CA, et al. A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda. Proc Natl Acad Sci. 2007;104:5079–5084.
   PubMed Web of Science ®Google Scholar
• Sinclair PR, Gorman N, Walton HS, et al. Cyp1a2 is essential in murine uroporphyria caused by hexachlorobenzene and iron. Toxicol Appl Pharmacol. 2000;162:60–67.
   PubMed Web of Science ®Google Scholar
• Ryan Caballes F, Sendi H, Bonkovsky HL, et al. porphyria cutanea tarda and liver iron: an update. Liver Int. 2012;32:880–893.
   PubMed Web of Science ®Google Scholar
• English JC, Peake MF, Becker LE. Hepatitis C and porphyria cutanea tarda. Cutis. 1996;57:404–408.
   PubMed Web of Science ®Google Scholar
• Thunell S, Harper P. Porphyrins, porphyrin metabolism, porphyrias. III. Diagnosis, care and monitoring in porphyria cutanea tarda–suggestions for a handling programme. Scand J Clin Lab Invest. 2000;60:561–579.
   PubMed Web of Science ®Google Scholar
• Grossman M, Bicker D, Poh-Fitzpatrick M, et al. Porphyria cutanea tarda☆ Clinical features and laboratory findings in 40 patients. Am J Med. 1979;67:2770286.
   Web of Science ®Google Scholar
• Tong Y, Song YK, Tyring S. Resolution of Porphyria Cutanea Tarda in Patients With Hepatitis C Following Ledipasvir-Sofosbuvir Combination Therapy. JAMA Dermatology. 2016;152:1393.
   PubMed Web of Science ®Google Scholar
• Singal AK, Venkata KVR, Jampana S, et al. Hepatitis C Treatment in Patients With Porphyria Cutanea Tarda. Am J Med Sci. 2017;353:523–528.
   PubMed Web of Science ®Google Scholar
• Crimlisk HL. The little imitator–porphyria: a neuropsychiatric disorder. J Neurol Neurosurg Psychiatry. 1997;62:319–328.
   PubMed Web of Science ®Google Scholar
• 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;91:1436–1444.
   PubMed Web of Science ®Google Scholar
• Meissner PN, Day RS, Moore MR, et al. Protoporphyrinogen oxidase and porphobilinogen deaminase in variegate porphyria. Eur J Clin Invest. 1986;16:257–261.
   PubMed Web of Science ®Google Scholar
• Eales L, Day RS, Blekkenhorst GH. The clinical and biochemical features of variegate porphyria: an analysis of 300 cases studied at Groote Schuur Hospital, Cape Town. Int J Biochem. 1980;12:837–853.
   PubMedGoogle Scholar
• Meissner PN, Dailey TA, Hift RJ, et al. A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria. Nat Genet. 1996;13:95–97.
   PubMed Web of Science ®Google Scholar
• Sandberg S, Romslo I. Porphyrin-induced photodamage at the cellular and the subcellular level as related to the solubility of the porphyrin. Clin Chim Acta. 1981;109:193–201.
   PubMed Web of Science ®Google Scholar
• Fujita H, Kondo M, Taketani S, … 1994 NN-H molecular, undefined. Characterization and expression of cDNA encoding coproporphyrinogen oxidase from a patient with hereditary coproporphyria. academic.oup.com.
   Google Scholar
• Brodie MJ, Thompson GG, Moore MR, et al. Hereditary coproporphyria. Demonstration of the abnormalities in haem biosynthesis in peripheral blood. Q J Med. 1977;46:229–241.
   PubMedGoogle Scholar
• Dsnick RJ, Astrin KH. Congenital erythropoietic porphyria: advances in pathogenesis and treatment. Br J Haematol. 2002;117:779–795.
   PubMed Web of Science ®Google Scholar
• Podlipnik S, Guijarro F, Combalia A, et al. Acquired erythropoietic uroporphyria secondary to myelodysplastic syndrome with chromosome 3 alterations: a case report. Br J Dermatol. 2018 Aug;179(2):486–490.
   Web of Science ®Google Scholar
• Di Pierro E, Brancaleoni V, Granata F. Advances in understanding the pathogenesis of congenital erythropoietic porphyria. Br J Haematol. 2016;173:365–379.
   PubMed Web of Science ®Google Scholar
• Murphy GM, Hawk JLM, Nicholson DC, et al. Congenital erythropoietic porphyria (Gunther’s disease). Clin Exp Dermatol. 1987;12:61–65.
   PubMed Web of Science ®Google Scholar
• De Verneuil H, Beaumont C, Deybach J-C, et al. Kastally2 R. enzymatic and immunological studies of uroporphyrinogen decarboxylase in familial porphyria cutanea tarda and hepatoerythropoietic porphyria. Am J Hum Genet. 1984;36:613–622.
   PubMed Web of Science ®Google Scholar
• Martinez Peinado C, Díaz de Heredia C, To-Figueras J, et al. Successful treatment of congenital erythropoietic porphyria using matched unrelated hematopoietic stem cell transplantation. Pediatr Dermatol. 2013;30:484–489.
   PubMed Web of Science ®Google Scholar
• Yien YY, Ducamp S, van der Vorm LN, et al. Mutation in human CLPX elevates levels of δ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria. Proc Natl Acad Sci U S A. 2017;114:E8045–52.
   PubMed Web of Science ®Google Scholar
• Livideanu CB, Ducamp S, Lamant L, et al. Late-onset X-linked dominant protoporphyria: an etiology of photosensitivity in the elderly. J Invest Dermatol. 2013;133:1688–1690.
   PubMed Web of Science ®Google Scholar
• Lecha M, Puy H, Deybach J-C. Erythropoietic protoporphyria. Orphanet J Rare Dis. 2009;4:19.
   PubMed Web of Science ®Google Scholar
• Thunell S, Harper P, Brun A. Porphyrins, porphyrin metabolism and porphyrias. IV. Pathophysiology of erythyropoietic protoporphyria–diagnosis, care and monitoring of the patient. Scand J Clin Lab Invest. 2000;60:581–604.
   PubMed Web of Science ®Google Scholar
• Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for Erythropoietic Protoporphyria. N Engl J Med. 2015;373:48–59.
   PubMed Web of Science ®Google Scholar
• Landefeld C, Kentouche K, Gruhn B, et al. X-linked protoporphyria: iron supplementation improves protoporphyrin overload, liver damage and anaemia. Br J Haematol. 2016;173:482–484.
   PubMed Web of Science ®Google Scholar
• Hodges VM, Rainey S, Lappin TR, et al. Pathophysiology of anemia and erythrocytosis. Crit Rev Oncol Hematol. 2007;64:139–158.
   PubMed Web of Science ®Google Scholar
• Holme SA, Worwood M, Anstey AV, et al. Erythropoiesis and iron metabolism in dominant erythropoietic protoporphyria. Blood. 2007;110:4108–4110.
   PubMed Web of Science ®Google Scholar
• Barman-Aksözen J, Minder EI, Schubiger C, et al. In ferrochelatase-deficient protoporphyria patients, ALAS2 expression is enhanced and erythrocytic protoporphyrin concentration correlates with iron availability. Blood Cells, Mol Dis. 2015;54:71–77.
   PubMed Web of Science ®Google Scholar
• Minder EI, Barman-Aksoezen J, Nydegger M, et al. Existing therapies and therapeutic targets for erythropoietic protoporphyria. Expert Opin Orphan Drugs. 2016;4:577–589.
   Web of Science ®Google Scholar
• Oustric V, Manceau H, Ducamp S, et al. Antisense oligonucleotide-based therapy in human erythropoietic protoporphyria. Am J Hum Genet. 2014;94:611–617.
   PubMed Web of Science ®Google Scholar
• Lamola AA, Piomelli S, Poh-Fitzpatrick MG, et al. 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.
   PubMed Web of Science ®Google Scholar
• Deybach J. Painful photosensitivity. Lancet. 2001;358:S49.
   PubMedGoogle Scholar
• Wachowska M, Muchowicz A, Firczuk M, et al. Aminolevulinic Acid (ALA) as a prodrug in photodynamic therapy of cancer. Mol 2011, Vol 16, Pages 4140-4164. 2011;16:4140–4164.
   Web of Science ®Google Scholar
• Gou EW, Phillips JD, Anderson KE. The porphyrias. In: Metabolic Diseases: Foundations of Clinical Management, Genetics, and Pathology (pp. 543–576). IOS Press; 2017. DOI: 10.3233/978-1-61499-718-4-577.
   Google Scholar
• Giunta A, Demin F, Campione E, et al. Dermatitis artefacta in sporadic sclerodermoid hepatitis C virus-associated porphyria cutanea tarda. J Eur Acad Dermatology Venereol. 2009;23:849–850.
   PubMed Web of Science ®Google Scholar
• Nelson JC, Westwood M, Allen KR, et al. The ratio of erythrocyte zinc-protoporphyrin to protoporphyrin IX in disease and its significance in the mechanism of lead toxicity on haem synthesis. Annals of Clinical Biochemistry. 1998 May;35(3):422–426.
   Google Scholar
• Lamola A, Yamane T. Zinc protoporphyrin in the erythrocytes of patients with lead intoxication and iron deficiency anemia. Science (80-). 1974;186:936–938.
   PubMed Web of Science ®Google Scholar
• Sandberg S, Brun A, Bjordal M, et al. Effect of zinc on protoporphyrin induced photohaemolysis. Scand J Clin Lab Invest. 1980;40:185–189.
   PubMed Web of Science ®Google Scholar
• Sandberg S, Talstad I, Høvding G, et al. Light-induced release of protoporphyrin, but not of zinc protoporphyrin, from erythrocytes in a patient with greatly elevated erythrocyte protoporphyrin. Blood. 1983;62:846–851.
   PubMed Web of Science ®Google Scholar
• Piomelli S, Lamola AA, Poh Fitzpatrick MB, et al. Erythropoietic protoporphyria and lead intoxication: the molecular basis for difference in cutaneous photosensitivity. I. Different rates of disappearance of protoporphyrin from the erythrocytes, both in vivo and in vitro. J Clin Invest. 1975;56:1519–1527.
   PubMed Web of Science ®Google Scholar
• Brun A, Sandberg S. Photodynamic release of protoporphyrin from intact erythrocytes in erythropoietic protoporphyria: the effect of small repetitive light doses. Photochem Photobiol. 1985;41:535–541.
   PubMed Web of Science ®Google Scholar
• Ratnaike S, Blake D. The diagnosis and follow-up of porphyria. Pathology. 1995;27:142–153.
   PubMed Web of Science ®Google Scholar
• Petersen AB, Philipsen PA, Wulf HC. Zinc sulphate: a new concept of treatment of erythropoietic protoporphyria. Br J Dermatol. 2012;166:1129–1131.
   PubMed Web of Science ®Google Scholar
• Brun A, Sandberg S, Høvding G, et al. Zinc as an oral photoprotective agent in erythropoietic protoporphyria?. International Journal of Biochemistry. 1980 Jan 1;12(5-6):931–934.
   Google Scholar
• Shehade S, Ead R, McDowell D, et al. Effects of oral zinc in erythropoietic protoporphyria. Arch Dermatol. 1989;125:1713.
   PubMedGoogle Scholar
• Petersen AB, Philipsen PA, Wulf HC. An explorative study of non-invasive ultra-weak photon emission and the anti-oxidative influence of oral zinc sulphate in light-sensitive patients with erythropoietic protoporphyria. Ski Res Technol. 2012;18:405–412.
   PubMed Web of Science ®Google Scholar