porphyrias

Summary

Summary: A diverse group of metabolic diseases characterized by errors in the biosynthetic pathway of HEME in the LIVER, the BONE MARROW, or both. They are classified by the deficiency of specific enzymes, the tissue site of enzyme defect, or the clinical features that include neurological (acute) or cutaneous (skin lesions). Porphyrias can be hereditary or acquired as a result of toxicity to the hepatic or erythropoietic marrow tissues.

Top Publications

  1. Aarsand A, Villanger J, Støle E, Deybach J, Marsden J, To Figueras J, et al. European specialist porphyria laboratories: diagnostic strategies, analytical quality, clinical interpretation, and reporting as assessed by an external quality assurance program. Clin Chem. 2011;57:1514-23 pubmed publisher
    The porphyrias are a group of rare metabolic disorders whose diagnosis depends on identification of specific patterns of porphyrin precursor and porphyrin accumulation in urine, blood, and feces...
  2. Deybach J, Badminton M, Puy H, Sandberg S, Frank J, Harper P, et al. European porphyria initiative (EPI): a platform to develop a common approach to the management of porphyrias and to promote research in the field. Physiol Res. 2006;55 Suppl 2:S67-73 pubmed
    b>Porphyrias are uncommon inherited diseases of haem biosynthesis for which the diagnosis and treatment varies in individual countries...
  3. Phillips J, Kushner J. Fast track to the porphyrias. Nat Med. 2005;11:1049-50 pubmed
  4. De Silva B, Banney L, Uttley W, Luqmani R, Schofield O. Pseudoporphyria and nonsteroidal antiinflammatory agents in children with juvenile idiopathic arthritis. Pediatr Dermatol. 2000;17:480-3 pubmed
    ..Blue/gray eye color was an independent risk factor for the development of pseudoporphyria. We would advise caution in prescribing naproxen in these children to prevent disfiguring facial scarring. ..
  5. Whatley S, Mason N, Woolf J, Newcombe R, Elder G, Badminton M. Diagnostic strategies for autosomal dominant acute porphyrias: retrospective analysis of 467 unrelated patients referred for mutational analysis of the HMBS, CPOX, or PPOX gene. Clin Chem. 2009;55:1406-14 pubmed publisher
  6. Bryant P, Lachman P. Pseudoporphyria secondary to non-steroidal anti-inflammatory drugs. Arch Dis Child. 2003;88:961 pubmed
  7. Hivnor C, Nosauri C, James W, POH FITZPATRICK M. Cyclosporine-induced pseudoporphyria. Arch Dermatol. 2003;139:1373-4 pubmed
  8. Silver E, Silver A, Silver D, McCalmont T. Pseudoporphyria induced by oral contraceptive pills. Arch Dermatol. 2003;139:227-8 pubmed
  9. LaDuca J, Bouman P, Gaspari A. Nonsteroidal antiinflammatory drug-induced pseudoporphyria: a case series. J Cutan Med Surg. 2002;6:320-6 pubmed
    ..suspicion with appropriate laboratory and histopathologic findings help to make this diagnosis, and exclude true porphyrias. Rechallenge with the offending drug to produce symptom relapse has been proposed to be helpful in confirming ..

More Information

Publications62

  1. Green J, Manders S. Pseudoporphyria. J Am Acad Dermatol. 2001;44:100-8 pubmed
    ..Medications, chronic renal failure/dialysis, excessive sun exposure and UVA radiation have all been reported to cause pseudoporphyria. Recognition, diagnosis, and appropriate management of pseudoporphyria are discussed. ..
  2. Maerker J, Harm A, Foeldvari I, Hoger P. [Naproxen-induced pseudoporphyria]. Hautarzt. 2001;52:1026-9 pubmed
    ..Both dermatologists and rheumatologists should be aware of the risk of naproxen-induced pseudoporphyria and discontinue therapy early in order to avoid scar formation in light-exposed areas. ..
  3. Lawrence S, Ramirez U, Selwood T, Stith L, Jaffe E. Allosteric inhibition of human porphobilinogen synthase. J Biol Chem. 2009;284:35807-17 pubmed publisher
    ..Data support the hypothesis that human PBGS hexamer stabilization may explain these side effects. The current work identifies allosteric ligands of human PBGS and, thus, identifies human PBGS as a medically relevant allosteric enzyme. ..
  4. Tremblay J, Veilleux B. Pseudoporphyria associated with hemodialysis treated with N-acetylcysteine. J Am Acad Dermatol. 2003;49:1189-90 pubmed
  5. Puy H, Gouya L, Deybach J. Porphyrias. Lancet. 2010;375:924-37 pubmed publisher
    Hereditary porphyrias are a group of eight metabolic disorders of the haem biosynthesis pathway that are characterised by acute neurovisceral symptoms, skin lesions, or both...
  6. Balwani M, Desnick R. The porphyrias: advances in diagnosis and treatment. Blood. 2012;120:4496-504 pubmed publisher
    The inborn errors of heme biosynthesis, the porphyrias, are 8 genetically distinct metabolic disorders that can be classified as "acute hepatic," "hepatic cutaneous," and "erythropoietic cutaneous" diseases...
  7. Jamani A, Pudek M, Schreiber W. Liquid-chromatographic assay of urinary porphobilinogen. Clin Chem. 1989;35:471-5 pubmed
    ..5 mumol/L). We used the new assay to measure PBG concentrations in the urine of two patients with latent porphyria. This method is more sensitive than spectrophotometric techniques currently used for measuring urinary PBG. ..
  8. Tutois S, Montagutelli X, Da Silva V, Jouault H, Rouyer Fessard P, Leroy Viard K, et al. Erythropoietic protoporphyria in the house mouse. A recessive inherited ferrochelatase deficiency with anemia, photosensitivity, and liver disease. J Clin Invest. 1991;88:1730-6 pubmed
    ..Despite the presence in the mouse of clinical and biochemical features infrequent in the human, this mutation may represent a model for the human disease, especially in its severe form. ..
  9. Bruchajzer E, Frydrych B, Szymanska J. Octabromodiphenyl ether - porphyrogenicity after repeated administration to rats. Int J Occup Med Environ Health. 2012;25:392-403 pubmed publisher
    ..5-10 fold. The study revealed that repeated exposure to OctaBDE affects heme biosynthesis and the levels of porphyrins. The lowest effective level which induced changes in porphyrin concentration was 2 mg/kg/day. ..
  10. Wang Y, Gatti P, Sadilek M, Scott C, Turecek F, Gelb M. Direct assay of enzymes in heme biosynthesis for the detection of porphyrias by tandem mass spectrometry. Uroporphyrinogen decarboxylase and coproporphyrinogen III oxidase. Anal Chem. 2008;80:2599-605 pubmed publisher
    ..066 +/- 0.009 microM). The assays show good reproducibility, use simple workup by liquid-liquid extraction of enzymatic products, and employ commercially available substrates and internal standards. ..
  11. Hanada S, Snider N, Brunt E, Hollenberg P, Omary M. Gender dimorphic formation of mouse Mallory-Denk bodies and the role of xenobiotic metabolism and oxidative stress. Gastroenterology. 2010;138:1607-17 pubmed publisher
    ..Gender dimorphic formation of MDBs and porphyria associate with differences in CYPs, oxidative injury, and selective keratin induction. These findings may extend to human MDBs and other neuropathy- and myopathy-related inclusions. ..
  12. de Bataille S, Dutartre H, Puy H, Deybach J, Gouya L, Raffray E, et al. Influence of meteorological data on sun tolerance in patients with erythropoietic protoporphyria in France. Br J Dermatol. 2016;175:768-75 pubmed publisher
    ..Patients were selected from the national record of the Centre Français des Porphyries (French Porphyrias referral centre)...
  13. Nakahashi Y, Fujita H, Taketani S, Ishida N, Kappas A, Sassa S. The molecular defect of ferrochelatase in a patient with erythropoietic protoporphyria. Proc Natl Acad Sci U S A. 1992;89:281-5 pubmed
    ..This point mutation appears to be responsible for the post-transcriptional splicing abnormality resulting in an aberrant transcript of ferrochelatase in this patient. ..
  14. Jaffe E, Stith L. ALAD porphyria is a conformational disease. Am J Hum Genet. 2007;80:329-37 pubmed
    ..We propose that the disequilibrium of morpheein assemblies broadens the definition of conformational diseases beyond the prion disorders and that ALAD porphyria is the first example of a morpheein-based conformational disease. ..
  15. Lamoril J, Boulechfar S, De Verneuil H, Grandchamp B, Nordmann Y, Deybach J. Human erythropoietic protoporphyria: two point mutations in the ferrochelatase gene. Biochem Biophys Res Commun. 1991;181:594-9 pubmed
    ..This EPP patient was then double heterozygous and as expected each of his parents carried one of the mutations. A second similar EPP patient was screened for these mutations with negative results, showing a genetic heterogeneity in EPP. ..
  16. De Verneuil H, Bourgeois F, de Rooij F, Siersema P, Wilson J, Grandchamp B, et al. Characterization of a new mutation (R292G) and a deletion at the human uroporphyrinogen decarboxylase locus in two patients with hepatoerythropoietic porphyria. Hum Genet. 1992;89:548-52 pubmed
    ..The possibility that the arginine 292 may participate at the active site of the enzyme is discussed. A summary of the 7 mutations/deletions found in the UROD gene with their frequency is presented. ..
  17. Markus R, Reddick M, Rubenstein M. Rofecoxib-induced pseudoporphyria. J Am Acad Dermatol. 2004;50:647-8 pubmed
  18. Chowdhury U, Patel K, Seth S, Ray R, Jagia P, Sahu M. Congenital Erythropoietic Porphyria With Calcific Constrictive Pericarditis: A Case Report and Brief Review of Literature. World J Pediatr Congenit Heart Surg. 2015;6:646-9 pubmed publisher
    ..The cause of pericardial calcification could be deposition of porphyrins in the pericardium. Surgical importance of this rare condition is highlighted. ..
  19. Aktuglu Zeybek A, Kiykim E, Cansever M. Hereditary Tyrosinemia Type 1 in Turkey. Adv Exp Med Biol. 2017;959:157-172 pubmed publisher
  20. Collantes M, Serrano Mendioroz I, Benito M, Molinet Dronda F, Delgado M, Vinaixa M, et al. Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency. Hum Mol Genet. 2016;25:1318-27 pubmed publisher
    ..Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver. ..
  21. Fukuda Y, Cheong P, Lynch J, Brighton C, Frase S, Kargas V, et al. The severity of hereditary porphyria is modulated by the porphyrin exporter and Lan antigen ABCB6. Nat Commun. 2016;7:12353 pubmed publisher
    Hereditary porphyrias are caused by mutations in genes that encode haem biosynthetic enzymes with resultant buildup of cytotoxic metabolic porphyrin intermediates...
  22. Levin K. Variants and mimics of Guillain Barré Syndrome. Neurologist. 2004;10:61-74 pubmed
    ..Appropriate diagnosis requires a combination of careful history and examination, and accurate interpretation of diagnostic testing. ..
  23. Schjelde S, Lund C. [Anaesthetics and porphyria]. Ugeskr Laeger. 2014;176: pubmed
    ..Acute porphyrias are rare inherited diseases caused by inefficient enzymatic activity within the haem synthesis...
  24. Poblete Gutierrez P, Kunitz O, Wolff C, Frank J. Diagnosis and treatment of the acute porphyrias: an interdisciplinary challenge. Skin Pharmacol Appl Skin Physiol. 2001;14:393-400 pubmed
    The porphyrias comprise a group of fascinating disorders resulting from predominantly inherited as well as acquired deficiencies of one of the eight enzymes along the pathway of heme biosynthesis...
  25. Llambías E, Aldonatti C, San Martín de Viale L. Tryptophan metabolism via serotonin in rats with hexachlorobenzene experimental porphyria. Biochem Pharmacol. 2003;66:35-42 pubmed
    ..The absence of neurological symptoms in patients with Porphyria Cutanea Tarda could be related to the absence of a statistically significant variation in serotonin content shown in brain. ..
  26. Zuijderhoudt F, Kamphuis J, Kluitenberg W, Dorresteijn de Bok J. Precision and accuracy of a HPLC method for measurement of fecal porphyrin concentrations. Clin Chem Lab Med. 2002;40:1036-9 pubmed
    ..The precision of porphyrin measurements was not influenced by the type of porphyria. Recoveries of added coproporphyrin and protoporphyrin were 90% and 108%; coefficients of variation were 6% and 19%, respectively. ..
  27. Chen B, Solis Villa C, Hakenberg J, Qiao W, Srinivasan R, Yasuda M, 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 publisher
    ..Thus, the estimated penetrance of acute attacks was ?1% of heterozygotes with likely-pathogenic mutations, highlighting the importance of predisposing/protective genes and environmental modifiers that precipitate/prevent the attacks. ..
  28. Todaka T, Uchi H, Hirakawa H, Takao Y, Kajiwara J, Furue M. The changes in dioxin concentrations in the blood of Yusho patients from 2004 to 2010. Fukuoka Igaku Zasshi. 2013;104:118-27 pubmed
    ..These findings suggest that the PCDDs, PCDFs, and PCBs have remained in the blood of Yusho patients for a very long time, with over 40 years having passed since the outbreak of Yusho. ..
  29. Cloutier G, Daronatand M, Savery D, Garcia D, Durand L, Foster F. Non-Gaussian statistics and temporal variations of the ultrasound signal backscattered by blood at frequencies between 10 and 58 MHz. J Acoust Soc Am. 2004;116:566-77 pubmed
  30. Adjarov D, Kerimova M. Effective control of patients with porphyria cutanea tarda by measuring plasma uroporphyrin. Clin Exp Dermatol. 1991;16:254-7 pubmed
    ..Retreatment is necessary when the levels exceed 23 nmol/l. The use of the method is recommended as a simple and effective way for monitoring the progress of patients with PCT. ..
  31. Solis Herruzo J, Pérez Peña F. [Erythropoietic protoporphyria (I. Clinical aspects and diagnosis)]. Rev Clin Esp. 1973;128:451-62 pubmed
  32. Vidaurre J, Gedela S, Yarosz S. Antiepileptic Drugs and Liver Disease. Pediatr Neurol. 2017;77:23-36 pubmed publisher
    ..Thus physicians should be mindful of the pharmacokinetic profile and the hepatotoxic potential of the different antiepileptic drugs available to treat patients affected by liver disease. ..
  33. Heinemann I, Jahn M, Jahn D. The biochemistry of heme biosynthesis. Arch Biochem Biophys. 2008;474:238-51 pubmed publisher
    ..Unusual and challenging biochemistry including tRNA-dependent reactions, radical SAM enzymes and substrate derived cofactors are reported. ..
  34. Hasegawa K, Tanaka H, Yamashita M, Higuchi Y, Miyai T, Yoshimoto J, et al. Neonatal-Onset Hereditary Coproporphyria: A New Variant of Hereditary Coproporphyria. JIMD Rep. 2017;37:99-106 pubmed publisher
    ..Based on genetic mutation of the CPOX gene and information from a previous similar case report, we consider that neonatal-onset HCP is a variant of HCP. ..
  35. Rigal J, Blanloeil Y. Anaesthesia and porphyria. Minerva Anestesiol. 2002;68:326-31 pubmed
  36. Kalivas J. Case 20-2008: Abdominal pain and weakness after gastric bypass surgery. N Engl J Med. 2008;359:1852; author reply 1852 pubmed
  37. Sies C, Florkowski C, George P, Potter H. Clinical indications for the investigation of porphyria: case examples and evolving laboratory approaches to its diagnosis in New Zealand. N Z Med J. 2005;118:U1658 pubmed
    ..Accurate screening and diagnosis of porphyria is important, as an acute porphyric attack is life-threatening and preventable. Retrospective diagnosis may be difficult. ..
  38. de Villiers J, Kotze M, van Heerden C, Sadie A, Gardner H, Liebenberg J, et al. Overrepresentation of the founder PPOX gene mutation R59W in a South African patient with severe clinical manifestation of porphyria. Exp Dermatol. 2005;14:50-5 pubmed
    ..A homozygote for the R59W mutation has never been detected, and the severe clinical manifestation observed in our patient is consistent with the hypothesis that such a genotype will not be compatible with life. ..
  39. Köstler E. [Definition and classification of porphyrias]. Z Gesamte Inn Med. 1987;42:528-30 pubmed
    ..An establishment of the well-known porphyrias is given, taking into consideration the first describers, the hereditary factors and first individual of ..
  40. Gamble J, Nakatsu K, Marks G. Porphyrinogenic xenobiotic-induced N-alkylprotoporphyrin IX formation: a bioassay utilizing chick embryo hepatic ferrochelatase. J Pharmacol Toxicol Methods. 2002;47:25-32 pubmed
    ..This would provide information both on the formation of N-alkylPPs and distinguish between those N-alkylPPs that produced porphyrin accumulation via FC inhibition and those that do not. ..
  41. Franklin M, Phillips J, Kushner J. Accelerated development of uroporphyria in mice heterozygous for a deletion at the uroporphyrinogen decarboxylase locus. J Biochem Mol Toxicol. 2001;15:287-93 pubmed
    ..From differences in the CO absorbance maximum, and by P450 activity analysis, this attenuated induction response resulted from an attenuation of the CYP2B not the CYP1A induction. ..
  42. Pierach C. Did Ulysses have porphyria?. J Lab Clin Med. 2004;144:7-10 pubmed
    ..well elucidated and errors along that route have been identified and firmly connected to specific diseases, the porphyrias, slight but nonspecific abnormalities, are occasionally invoked as proof of porphyria or in support of other ..
  43. De Siervi A, Mendez M, Parera V, Varela L, Batlle A, Rossetti M. Acute intermittent porphyria: characterization of two novel mutations in the porphobilinogen deaminase gene, one amino acid deletion (453-455delAGC) and one splicing aceptor site mutation (IVS8-1G>T). Hum Mutat. 1999;14:355 pubmed
    ..coli, the enzymatic activity of the recombinant protein was 1.3% of the mean level expressed by the normal allele. Finally, three missense mutations, previously reported, were identified in three unrelated families. ..
  44. Sah J, Ito H, Kolli B, Peterson D, Sassa S, Chang K. Genetic rescue of Leishmania deficiency in porphyrin biosynthesis creates mutants suitable for analysis of cellular events in uroporphyria and for photodynamic therapy. J Biol Chem. 2002;277:14902-9 pubmed
    ..Monocytic tumor cells were rendered photosensitive by infection with uroporphyric Leishmania, suggestive of their potential application for photodynamic therapy. ..
  45. Gentile S, Ayala F, Orlando C, Santoianni P, Budillon G. Effect of nicotinic acid administration on serum levels of bilirubin and iron in patients with porphyria cutanea tarda. Scand J Clin Lab Invest. 1988;48:641-5 pubmed
    ..The latter being probably the consequence of an enhanced excretion of iron extraproduced by the haemolytic effect of NA. ..
  46. Bonkovsky H, Siao P, Roig Z, Hedley Whyte E, Flotte T. Case records of the Massachusetts General Hospital. Case 20-2008. A 57-year-old woman with abdominal pain and weakness after gastric bypass surgery. N Engl J Med. 2008;358:2813-25 pubmed publisher
  47. Schad S, Kraus A, Haubitz I, Trcka J, Hamm H, Girschick H. Early onset pauciarticular arthritis is the major risk factor for naproxen-induced pseudoporphyria in juvenile idiopathic arthritis. Arthritis Res Ther. 2007;9:R10 pubmed
    ..JIA disease activity seems to be a confounding factor for PP. In particular, patients with early-onset pauciarticular JIA patients who have significant inflammation appear to be prone to developing PP upon treatment with naproxen. ..
  48. Kwong W, Hsu S. Pseudoporphyria associated with voriconazole. J Drugs Dermatol. 2007;6:1042-4 pubmed
    ..Voriconazole was not discontinued due to medical necessity. The patient's pseudoporphyria was adequately controlled with UVA and UVB protection sunscreen despite continued mild sun exposure. ..
  49. Hindmarsh J, Oliveras L, Greenway D. Biochemical differentiation of the porphyrias. Clin Biochem. 1999;32:609-19 pubmed
    To differentiate the porphyrias by clinical and biochemical methods. We describe levels of blood, urine, and fecal porphyrins and their precursors in the porphyrias and present an algorithm for their biochemical differentiation...
  50. Chung J, Anderson S, Gwynn B, Deck K, Chen M, Langer N, et al. Iron regulatory protein-1 protects against mitoferrin-1-deficient porphyria. J Biol Chem. 2014;289:7835-43 pubmed publisher
    ..Together, our data support a model whereby impaired mitochondrial [Fe-S] cluster biogenesis in Mfrn1(gt/gt) cells results in elevated IRP1 RNA-binding that attenuates ALAS2 mRNA translation and protoporphyrin accumulation. ..
  51. Elder G, Roberts A. Uroporphyrinogen decarboxylase. J Bioenerg Biomembr. 1995;27:207-14 pubmed
    ..Two related human porphyrias, porphyria cutanea tarda and hepatoerythropoietic porphyria, also result from deficiency of this enzyme...
  52. De Matteis F, Harvey C, Reed C, Hempenius R. Increased oxidation of uroporphyrinogen by an inducible liver microsomal system. Possible relevance to drug-induced uroporphyria. Biochem J. 1988;250:161-9 pubmed
  53. Zheng J, Tian Q, Hou W, Watts J, Schrum L, Bonkovsky H. Tissue-specific expression of ALA synthase-1 and heme oxygenase-1 and their expression in livers of rats chronically exposed to ethanol. FEBS Lett. 2008;582:1829-34 pubmed publisher
    ..These results provide novel insights into the effects of chronic ethanol consumption on hepatic heme biosynthesis and porphyrias.