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Semin Liver Dis 2024; 44(02): 209-225
DOI: 10.1055/s-0044-1787076
Review Article

Understanding Hepatic Porphyrias: Symptoms, Treatments, and Unmet Needs

Oluwashanu Balogun
1   Department of Experimental Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
,
Kari Nejak-Bowen
1   Department of Experimental Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
2   Pittsburgh Liver Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
› Institutsangaben Funding This study was funded by NIH grant 1R01DK124412 to K.N-B.
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Abstract

Hepatic porphyrias are a group of metabolic disorders that are characterized by overproduction and accumulation of porphyrin precursors in the liver. These porphyrins cause neurologic symptoms as well as cutaneous photosensitivity, and in some cases patients can experience life-threatening acute neurovisceral attacks. This review describes the acute hepatic porphyrias in detail, including acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, as well as the hepatic porphyrias with cutaneous manifestations such as porphyria cutanea tarda and hepatoerythropoietic porphyria. Each section will cover disease prevalence, clinical manifestations, and current therapies, including strategies to manage symptoms. Finally, we review new and emerging treatment modalities, including gene therapy through use of adeno-associated vectors and chaperone therapies such as lipid nanoparticle and small interfering RNA-based therapeutics.

Keywords

acute intermittent porphyria - hereditary coproporphyria - variegate porphyria - porphyria cutanea tarda - hepatoerythropoietic porphyria

Supplementary Material



Publikationsverlauf

Artikel online veröffentlicht:
17. Mai 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.

 

  • References

  • 1 Puy H, Gouya L, Deybach JC. Porphyrias. Lancet 2010; 375 (9718) 924-937
    CrossrefPubMedGoogle Scholar
  • 2 Anderson KE, Sassa SS, Bishop DF. et al. Disorders of heme biosynthesis: X-linked sideroblastic anemia and the porphyrias. In: Scriver CR, Beaudet AL, Sly WS. et al, eds, The Metabolic Basis of Inherited Disease. 8th ed. New York:: McGraw-Hill;; 2001
    Google Scholar
  • 3 Karim Z, Lyoumi S, Nicolas G, Deybach JC, Gouya L, Puy H. Porphyrias: A 2015 update. Clin Res Hepatol Gastroenterol 2015; 39 (04) 412-425
    CrossrefPubMedGoogle Scholar
  • 4 Balwani M, Desnick RJ. The porphyrias: advances in diagnosis and treatment. Blood 2012; 120 (23) 4496-4504
    CrossrefPubMedGoogle Scholar
  • 5 Balogun O, Nejak-Bowen K. The hepatic porphyrias: revealing the complexities of a rare disease. Semin Liver Dis 2023; 43 (04) 446-459
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 6 Ajioka RS, Phillips JD, Weiss RB. et al. Down-regulation of hepcidin in porphyria cutanea tarda. Blood 2008; 112 (12) 4723-4728
    CrossrefPubMedGoogle Scholar
  • 7 Phillips JD. Heme biosynthesis and the porphyrias. Mol Genet Metab 2019; 128 (03) 164-177
    CrossrefPubMedGoogle Scholar
  • 8 Ajioka RS, Phillips JD, Kushner JP. Biosynthesis of heme in mammals. Biochim Biophys Acta 2006; 1763 (07) 723-736
    CrossrefPubMedGoogle Scholar
  • 9 Ogun AS, Joy NV, Valentine M. . Biochemistry, Heme Synthesis. Treasure Island (FL): StatPearls; 2024
  • 10 Dailey HA, Meissner PN. Erythroid heme biosynthesis and its disorders. Cold Spring Harb Perspect Med 2013; 3 (04) a011676
    CrossrefPubMedGoogle Scholar
  • 11 Anderson KE. Porphyrias: an overview. In: Connor R. , ed, UpToDate. Waltham, MA: . Accessed on April 15, 2024. AT: https://www.uptodate.com/contents/porphyrias-an-overview
    Google Scholar
  • 12 Schultz IJ, Chen C, Paw BH, Hamza I. Iron and porphyrin trafficking in heme biogenesis. J Biol Chem 2010; 285 (35) 26753-26759
    CrossrefPubMedGoogle Scholar
  • 13 Peoc’h K, Nicolas G, Schmitt C. et al. Regulation and tissue-specific expression of δ-aminolevulinic acid synthases in non-syndromic sideroblastic anemias and porphyrias. Mol Genet Metab 2019; 128 (03) 190-197
    CrossrefPubMedGoogle Scholar
  • 14 Elbirt KK, Bonkovsky HL. Heme oxygenase: recent advances in understanding its regulation and role. Proc Assoc Am Physicians 1999; 111 (05) 438-447
    CrossrefPubMedGoogle Scholar
  • 15 America Porphyria Foundation. Types of Porphyria. 2010–2022
    PubMedGoogle Scholar
  • 16 Warren MJSAG. Tetrapyrroles Birth, Life and Death. New York, NY:: Springer;; 2009
    CrossrefGoogle Scholar
  • 17 Doss M, Look D, Henning H. et al. Hepatic porphyrins and urinary porphyrins and porphyrin precursors in liver cirrhosis. Klin Wochenschr 1972; 50 (22) 1025-1032
    CrossrefPubMedGoogle Scholar
  • 18 Maruno M, Furuyama K, Akagi R. et al. Highly heterogeneous nature of delta-aminolevulinate dehydratase (ALAD) deficiencies in ALAD porphyria. Blood 2001; 97 (10) 2972-2978
    CrossrefPubMedGoogle Scholar
  • 19 Ramanujam V-MS, Anderson KE. Porphyria diagnostics-Part 1: a brief overview of the porphyrias. Curr Protoc Hum Genet 2015;86:17.20.1117.20.26
    PubMedGoogle Scholar
  • 20 Mohan G, Madan A. Ala Dehydratase Deficiency Porphyria. Treasure Island (FL):: StatPearls Publishing;; 2023
    Google Scholar
  • 21 Kappas A. The porphyrias. In: The Metabolic and Molecular Basis of Inherited Disease. 7th ed. 1995: 2103-2159
    Google Scholar
  • 22 Akagi R, Kato N, Inoue R, Anderson KE, Jaffe EK, Sassa S. delta-Aminolevulinate dehydratase (ALAD) porphyria: the first case in North America with two novel ALAD mutations. Mol Genet Metab 2006; 87 (04) 329-336
    CrossrefPubMedGoogle Scholar
  • 23 Meyer UA, Schuurmans MM, Lindberg RL. Acute porphyrias: pathogenesis of neurological manifestations. Semin Liver Dis 1998; 18 (01) 43-52
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 24 Edel Y, Mamet R. Porphyria: what is it and who should be evaluated?. Rambam Maimonides Med J 2018; 9 (02) 9
    CrossrefPubMedGoogle Scholar
  • 25 Desnick RJ, Balwani M, Anderson KE. 10 - Inherited Porphyrias. In: Pyeritz RE, Korf BR, Grody WW. eds, Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics. 7th ed. Academic Press; 2021: 373-411
    Google Scholar
  • 26 Paller A, Mancini A. Photosensitivity and photoreactions. In: Hurwitz Clinical Pediatric Dermatology;. 2016: 448-466.e4
    Google Scholar
  • 27 Mustajoki P, Desnick RJ. Genetic heterogeneity in acute intermittent porphyria: characterisation and frequency of porphobilinogen deaminase mutations in Finland. Br Med J (Clin Res Ed) 1985; 291 (6494) 505-509
    CrossrefPubMedGoogle Scholar
  • 28 Brennan MJW, Cantrill RC. δ-aminolaevulinic acid is a potent agonist for GABA autoreceptors. Nature 1979; 280 (5722) 514-515
    CrossrefPubMedGoogle Scholar
  • 29 Mustajoki P, Koskelo P. Hereditary hepatic porphyrias in Finland. Acta Med Scand 1976; 200 (03) 171-178
    CrossrefPubMedGoogle Scholar
  • 30 Lenglet H, Schmitt C, Grange T. et al. From a dominant to an oligogenic model of inheritance with environmental modifiers in acute intermittent porphyria. Hum Mol Genet 2018; 27 (07) 1164-1173
    CrossrefPubMedGoogle Scholar
  • 31 Floderus Y, Shoolingin-Jordan PM, Harper P. Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene. Clin Genet 2002; 62 (04) 288-297
    CrossrefPubMedGoogle Scholar
  • 32 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 (11) 1215-1222
    CrossrefPubMedGoogle Scholar
  • 33 Whatley SD, Roberts AG, Llewellyn DH, Bennett CP, Garrett C, Elder GH. Non-erythroid form of acute intermittent porphyria caused by promoter and frameshift mutations distant from the coding sequence of exon 1 of the HMBS gene. Hum Genet 2000; 107 (03) 243-248
    CrossrefPubMedGoogle Scholar
  • 34 Bissell DM, Wang B. Acute hepatic porphyria. J Clin Transl Hepatol 2015; 3 (01) 17-26
    CrossrefPubMedGoogle Scholar
  • 35 Whatley SD, Badminton MN. Acute intermittent porphyria. In: Adam MP, Mirzaa GM, Pagon RA. , et al, eds, GeneReviews. Seattle (WA): University of Washington;; 1993
    Google Scholar
  • 36 Jericó D, Luis EO, Cussó L. et al. Brain ventricular enlargement in human and murine acute intermittent porphyria. Hum Mol Genet 2020; 29 (19) 3211-3223
    PubMedGoogle Scholar
  • 37 Gonzalez-Mosquera LF, Sonthalia S. Acute Intermittent Porphyria. Treasure Island (FL):: StatPearls Publishing;; 2023
    Google Scholar
  • 38 O'Malley R, Rao G, Stein P, Bandmann O. Porphyria: often discussed but too often missed. Pract Neurol 2018; 18 (05) 352-358
    CrossrefPubMedGoogle Scholar
  • 39 Innala E, Andersson C. Screening for hepatocellular carcinoma in acute intermittent porphyria: a 15-year follow-up in northern Sweden. J Intern Med 2011; 269 (05) 538-545
    CrossrefPubMedGoogle Scholar
  • 40 Wang B, Bissell DM. Hereditary coproporphyria. In: Adam MP, Everman DB, Mirzaa GM. , et al, eds, GeneReviews. Seattle (WA):: University of Washington, Seattle;; 1993
    Google Scholar
  • 41 Tchernitchko D, Tavernier Q, Lamoril J. et al. A variant of peptide transporter 2 predicts the severity of porphyria-associated kidney disease. J Am Soc Nephrol 2017; 28 (06) 1924-1932
    CrossrefPubMedGoogle Scholar
  • 42 Gugig R, Rosenthal P. Porphyria. In: Aminoff MJ, Daroff RB. eds, Encyclopedia of the Neurological Sciences. New York:: Academic Press;; 2003: 26-34
    Google Scholar
  • 43 Anderson KE, Collins S. Open-label study of hemin for acute porphyria: clinical practice implications. Am J Med 2006; 119 (09) 801.e19-801.e24
    CrossrefPubMedGoogle Scholar
  • 44 Fontanellas A, Ávila MA, Anderson KE, Deybach JC. Current and innovative emerging therapies for porphyrias with hepatic involvement. J Hepatol 2019; 71 (02) 422-433
    CrossrefPubMedGoogle Scholar
  • 45 Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. N Engl J Med 2017; 377 (09) 862-872
    CrossrefPubMedGoogle Scholar
  • 46 Ricci A, Ventura P. Givosiran for the treatment of acute hepatic porphyria. Expert Rev Clin Pharmacol 2022; 15 (04) 383-393
    CrossrefPubMedGoogle Scholar
  • 47 Soonawalla ZF, Orug T, Badminton MN. et al. Liver transplantation as a cure for acute intermittent porphyria. Lancet 2004; 363 (9410) 705-706
    CrossrefPubMedGoogle Scholar
  • 48 Wahlin S, Harper P, Sardh E, Andersson C, Andersson DE, Ericzon BG. Combined liver and kidney transplantation in acute intermittent porphyria. Transpl Int 2010; 23 (06) e18-e21
    CrossrefPubMedGoogle Scholar
  • 49 Yasuda M, Gan L, Chen B. et al. Homozygous hydroxymethylbilane synthase knock-in mice provide pathogenic insights into the severe neurological impairments present in human homozygous dominant acute intermittent porphyria. Hum Mol Genet 2019; 28 (11) 1755-1767
    CrossrefPubMedGoogle Scholar
  • 50 Ma E, Mar V, Varigos G, Nicoll A, Ross G. Haem arginate as effective maintenance therapy for hereditary coproporphyria. Australas J Dermatol 2011; 52 (02) 135-138
    CrossrefPubMedGoogle Scholar
  • 51 Elder G, Harper P, Badminton M, Sandberg S, Deybach JC. The incidence of inherited porphyrias in Europe. J Inherit Metab Dis 2013; 36 (05) 849-857
    CrossrefPubMedGoogle Scholar
  • 52 Blake D, McManus J, Cronin V, Ratnaike S. Fecal coproporphyrin isomers in hereditary coproporphyria. Clin Chem 1992; 38 (01) 96-100
    CrossrefPubMedGoogle Scholar
  • 53 Towns C, Balakrishnan S, Florkowski C, Davies A, Barrington-Ward E. High penetrance, recurrent attacks and thrombus formation in a family with hereditary coproporphyria. JIMD Rep 2022; 63 (03) 211-215
    CrossrefPubMedGoogle Scholar
  • 54 Kühnel A, Gross U, Doss MO. Hereditary coproporphyria in Germany: clinical-biochemical studies in 53 patients. Clin Biochem 2000; 33 (06) 465-473
    CrossrefPubMedGoogle Scholar
  • 55 Balwani M, Sardh E, Ventura P. et al; ENVISION Investigators. Phase 3 trial of RNAi therapeutic givosiran for acute intermittent porphyria. N Engl J Med 2020; 382 (24) 2289-2301
    CrossrefPubMedGoogle Scholar
  • 56 Logan GM, Weimer MK, Ellefson M, Pierach CA, Bloomer JR. Bile porphyrin analysis in the evaluation of variegate porphyria. N Engl J Med 1991; 324 (20) 1408-1411
    CrossrefPubMedGoogle Scholar
  • 57 Ferrer MD, Tauler P, Sureda A, Palacín C, Tur JA, Pons A. Antioxidants restore protoporphyrinogen oxidase in variegate porphyria patients. Eur J Clin Invest 2013; 43 (07) 668-678
    CrossrefPubMedGoogle Scholar
  • 58 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 (5-6): 837-853
    CrossrefPubMedGoogle Scholar
  • 59 von und zu Fraunberg M, Timonen K, Mustajoki P, Kauppinen R. Clinical and biochemical characteristics and genotype-phenotype correlation in Finnish variegate porphyria patients. Eur J Hum Genet 2002; 10 (10) 649-657
    CrossrefPubMedGoogle Scholar
  • 60 Long C, Smyth SJ, Woolf J. et al. Detection of latent variegate porphyria by fluorescence emission spectroscopy of plasma. Br J Dermatol 1993; 129 (01) 9-13
    CrossrefPubMedGoogle Scholar
  • 61 Pinder VA, Holden ST, Deshpande C. et al. Homozygous variegate porphyria presenting with developmental and language delay in childhood. Clin Exp Dermatol 2013; 38 (07) 737-740
    CrossrefPubMedGoogle Scholar
  • 62 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 (01) 95-97
    CrossrefPubMedGoogle Scholar
  • 63 Singal AK, Anderson KE. Variegate porphyria. In: GeneReviews [Internet]. Seattle, WA:: University of Washington;; 2013
    Google Scholar
  • 64 William DJ, Elston DM, Treat JR, Rosenbach MA. Andrews' Diseases of the Skin. 13th ed. Elsevier Inc;; 2020: 515-546
    Google Scholar
  • 65 Patterson JW. Metabolic and storage diseases. In: Weedon's Skin Pathology. 5th ed. Elsevier Limited;; 2010: 593-616
    Google Scholar
  • 66 Schulenburg-Brand D, Gardiner T, Guppy S. et al. An audit of the use of gonadorelin analogues to prevent recurrent acute symptoms in patients with acute porphyria in the United Kingdom. JIMD Rep 2017; 36: 99-107
    CrossrefPubMedGoogle Scholar
  • 67 Marsden JT, Guppy S, Stein P. et al. Audit of the use of regular haem arginate infusions in patients with acute porphyria to prevent recurrent symptoms. JIMD Rep 2015; 22: 57-65
    CrossrefPubMedGoogle Scholar
  • 68 Schneider-Yin X, van Tuyll van Serooskerken AM, Went P. et al. Hepatocellular carcinoma in variegate porphyria: a serious complication. Acta Derm Venereol 2010; 90 (05) 512-515
    CrossrefPubMedGoogle Scholar
  • 69 Singal AK. Porphyria cutanea tarda: recent update. Mol Genet Metab 2019; 128 (03) 271-281
    CrossrefPubMedGoogle Scholar
  • 70 Toussi A, Le ST, Merleev AA. et al. Porphyria cutanea tarda presenting as a lichenoid eruption. Photodermatol Photoimmunol Photomed 2021; 37 (03) 233-235
    CrossrefPubMedGoogle Scholar
  • 71 de Verneuil H, Aitken G, Nordmann Y. Familial and sporadic porphyria cutanea: two different diseases. Hum Genet 1978; 44 (02) 145-151
    CrossrefPubMedGoogle Scholar
  • 72 Elder GH, Lee GB, Tovey JA. Decreased activity of hepatic uroporphyrinogen decarboxylase in sporadic porphyria cutanea tarda. N Engl J Med 1978; 299 (06) 274-278
    CrossrefPubMedGoogle Scholar
  • 73 Bonkovsky HL, Lambrecht RW, Shan Y. Iron as a co-morbid factor in nonhemochromatotic liver disease. Alcohol 2003; 30 (02) 137-144
    CrossrefPubMedGoogle Scholar
  • 74 Bonkovsky HL, Poh-Fitzpatrick M, Pimstone N. et al. Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North America. Hepatology 1998; 27 (06) 1661-1669
    CrossrefPubMedGoogle Scholar
  • 75 Muñoz-Santos C, Guilabert A, Moreno N. et al. Familial and sporadic porphyria cutanea tarda: clinical and biochemical features and risk factors in 152 patients. Medicine (Baltimore) 2010; 89 (02) 69-74
    CrossrefPubMedGoogle Scholar
  • 76 Handler NS, Handler MZ, Stephany MP, Handler GA, Schwartz RA. Porphyria cutanea tarda: an intriguing genetic disease and marker. Int J Dermatol 2017; 56 (06) e106-e117
    CrossrefPubMedGoogle Scholar
  • 77 McColl KE, Moore MR, Thompson GG, Goldberg A. Abnormal haem biosynthesis in chronic alcoholics. Eur J Clin Invest 1981; 11 (06) 461-468
    CrossrefPubMedGoogle Scholar
  • 78 Fontanellas A, Martínez-Fresno M, Garrido-Astray MC. et al. Smoking but not homozygosity for CYP1A2 g-163A allelic variant leads to earlier disease onset in patients with sporadic porphyria cutanea tarda. Exp Dermatol 2010; 19 (08) e326-e328
    CrossrefPubMedGoogle Scholar
  • 79 Cruz-Rojo J, Fontanellas A, Morán-Jiménez MJ. et al. Precipitating/aggravating factors of porphyria cutanea tarda in Spanish patients. Cell Mol Biol 2002; 48 (08) 845-852
    PubMedGoogle Scholar
  • 80 Quansah R, Cooper CJ, Said S, Bizet J, Paez D, Hernandez GT. Hepatitis C- and HIV-induced porphyria cutanea tarda. Am J Case Rep 2014; 15: 35-40
    CrossrefPubMedGoogle Scholar
  • 81 Nishina S, Hino K, Korenaga M. et al. Hepatitis C virus-induced reactive oxygen species raise hepatic iron level in mice by reducing hepcidin transcription. Gastroenterology 2008; 134 (01) 226-238
    CrossrefPubMedGoogle Scholar
  • 82 Cruz MJ, Alves S, Baudrier T, Azevedo F. Porphyria cutanea tarda induced by tamoxifen. Dermatol Online J 2010; 16 (09) 2
    PubMedGoogle Scholar
  • 83 Bulaj ZJ, Franklin MR, Phillips JD. et al. Transdermal estrogen replacement therapy in postmenopausal women previously treated for porphyria cutanea tarda. J Lab Clin Med 2000; 136 (06) 482-488
    CrossrefPubMedGoogle Scholar
  • 84 Roenigk Jr HH, Gottlob ME. Estrogen-induced porphyria cutanea tarda. Report of three cases. Arch Dermatol 1970; 102 (03) 260-266
    CrossrefPubMedGoogle Scholar
  • 85 Gibson GE, McEvoy MT. Coexistence of lupus erythematosus and porphyria cutanea tarda in fifteen patients. J Am Acad Dermatol 1998; 38 (04) 569-573
    CrossrefPubMedGoogle Scholar
  • 86 Rodrigues N, Caeiro F, Santana A, Mendes T, Lopes L. Porphyria cutanea tarda in a patient with end-stage renal disease: a case of successful treatment with deferoxamine and ferric carboxymaltose. Case Rep Nephrol 2017; 2017: 4591871
    PubMedGoogle Scholar
  • 87 Christiansen AL, Bygum A, Hother-Nielsen O, Rasmussen LM. Diagnosing diabetes mellitus in patients with porphyria cutanea tarda. Int J Dermatol 2018; 57 (07) 763-769
    CrossrefPubMedGoogle Scholar
  • 88 McKenna DB, Browne M, O'Donnell R, Murphy GM. Porphyria cutanea tarda and hematologic malignancy–a report of 4 cases. Photodermatol Photoimmunol Photomed 1997; 13 (04) 143-146
    CrossrefPubMedGoogle Scholar
  • 89 Rudnick S, Phillips J, Bonkovsky H. et al. Familial porphyria cutanea tarda. In: Adam MP, Mirzaa GM, Pagon RA. , et al, eds, GeneReviews. Seattle, WA:: University of Washington;; 1993
    Google Scholar
  • 90 Ryan Caballes F, Sendi H, Bonkovsky HL. Hepatitis C, porphyria cutanea tarda and liver iron: an update. Liver Int 2012; 32 (06) 880-893
    CrossrefPubMedGoogle Scholar
  • 91 Ellervik C, Birgens H, Tybjaerg-Hansen A, Nordestgaard BG. Hemochromatosis genotypes and risk of 31 disease endpoints: meta-analyses including 66,000 cases and 226,000 controls. Hepatology 2007; 46 (04) 1071-1080
    CrossrefPubMedGoogle Scholar
  • 92 Berenguer J, Blasco J, Cardenal C. et al. Hepatoerythropoietic porphyria: neuroimaging findings. AJNR Am J Neuroradiol 1997; 18 (08) 1557-1560
    PubMedGoogle Scholar
  • 93 de Verneuil H, Beaumont C, Deybach JC, Nordmann Y, Sfar Z, Kastally R. Enzymatic and immunological studies of uroporphyrinogen decarboxylase in familial porphyria cutanea tarda and hepatoerythropoietic porphyria. Am J Hum Genet 1984; 36 (03) 613-622
    PubMedGoogle Scholar
  • 94 Rudnick S, Phillips J, Bonkovsky H. et al. Hepatoerythropoietic Porphyria. In: Adam MP, Mirzaa GM, Pagon RA. , et al, eds, GeneReviews. Seattle (WA):: University of Washington;; 1993
    Google Scholar
  • 95 Cantatore-Francis JL, Cohen-Pfeffer J, Balwani M. et al. Hepatoerythropoietic porphyria misdiagnosed as child abuse: cutaneous, arthritic, and hematologic manifestations in siblings with a novel UROD mutation. Arch Dermatol 2010; 146 (05) 529-533
    CrossrefPubMedGoogle Scholar
  • 96 Elder GH. Hepatic porphyrias in children. J Inherit Metab Dis 1997; 20 (02) 237-246
    CrossrefPubMedGoogle Scholar
  • 97 Anderson KE, Bloomer JR, Bonkovsky HL. et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005; 142 (06) 439-450
    CrossrefPubMedGoogle Scholar
  • 98 Marcacci M, Ricci A, Cuoghi C, Marchini S, Pietrangelo A, Ventura P. Challenges in diagnosis and management of acute hepatic porphyrias: from an uncommon pediatric onset to innovative treatments and perspectives. Orphanet J Rare Dis 2022; 17 (01) 160
    CrossrefPubMedGoogle Scholar
  • 99 Buttery JE. Is the Watson-Schwartz screening method for porphobilinogen reliable?. Clin Chem 1995; 41 (11) 1670-1671
    CrossrefPubMedGoogle Scholar
  • 100 Thadani H, Deacon A, Peters T. Diagnosis and management of porphyria. BMJ 2000; 320 (7250) 1647-1651
    CrossrefPubMedGoogle Scholar
  • 101 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 (12) 1233-1241
    CrossrefPubMedGoogle Scholar
  • 102 Andersen J, Thomsen J, Enes AR, Sandberg S, Aarsand AK. Health-related quality of life in porphyria cutanea tarda: a cross-sectional registry based study. Health Qual Life Outcomes 2020; 18 (01) 84
    CrossrefPubMedGoogle Scholar
  • 103 Mustajoki P, Nordmann Y. Early administration of heme arginate for acute porphyric attacks. Arch Intern Med 1993; 153 (17) 2004-2008
    CrossrefPubMedGoogle Scholar
  • 104 Kuter DJ, Bonkovsky HL, Monroy S. et al; ENVISION Investigators. Efficacy and safety of givosiran for acute hepatic porphyria: Final results of the randomized phase III ENVISION trial. J Hepatol 2023; 79 (05) 1150-1158
    CrossrefPubMedGoogle Scholar
  • 105 Massachi S, Epstein J, Hurd J, Bonkovsky HL. Cost savings with hemin versus givosiran for the treatment of patients with acute intermittent porphyria (AIP). J Med Econ 2020; 23 (12) 1441-1449
    CrossrefPubMedGoogle Scholar
  • 106 Willandt B, Langendonk JG, Biermann K. et al. Liver fibrosis associated with iron accumulation due to long-term heme-arginate treatment in acute intermittent porphyria: a case series. JIMD Rep 2016; 25: 77-81
    CrossrefPubMedGoogle Scholar
  • 107 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 (01) 78-91
    CrossrefPubMedGoogle Scholar
  • 108 To-Figueras J, Wijngaard R, García-Villoria J. et al. Dysregulation of homocysteine homeostasis in acute intermittent porphyria patients receiving heme arginate or givosiran. J Inherit Metab Dis 2021; 44 (04) 961-971
    CrossrefPubMedGoogle Scholar
  • 109 Longo M, Paolini E, Meroni M, Dongiovanni P. Cutting-edge therapies and novel strategies for acute intermittent porphyria: step-by-step towards the solution. Biomedicines 2022; 10 (03) 10
    CrossrefPubMedGoogle Scholar
  • 110 Yasuda M, Bishop DF, Fowkes M, Cheng SH, Gan L, Desnick RJ. AAV8-mediated gene therapy prevents induced biochemical attacks of acute intermittent porphyria and improves neuromotor function. Mol Ther 2010; 18 (01) 17-22
    CrossrefPubMedGoogle Scholar
  • 111 Unzu C, Sampedro A, Mauleón I. et al. Sustained enzymatic correction by rAAV-mediated liver gene therapy protects against induced motor neuropathy in acute porphyria mice. Mol Ther 2011; 19 (02) 243-250
    CrossrefPubMedGoogle Scholar
  • 112 Unzu C, Sampedro A, Mauleón I. et al. Porphobilinogen deaminase over-expression in hepatocytes, but not in erythrocytes, prevents accumulation of toxic porphyrin precursors in a mouse model of acute intermittent porphyria. J Hepatol 2010; 52 (03) 417-424
    CrossrefPubMedGoogle Scholar
  • 113 D'Avola D, López-Franco E, Sangro B. et al. Phase I open label liver-directed gene therapy clinical trial for acute intermittent porphyria. J Hepatol 2016; 65 (04) 776-783
    CrossrefPubMedGoogle Scholar
  • 114 Meliani A, Boisgerault F, Hardet R. et al. Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration. Nat Commun 2018; 9 (01) 4098
    CrossrefPubMedGoogle Scholar
  • 115 Serrano-Mendioroz I, Sampedro A, Serna N. et al. Bioengineered PBGD variant improves the therapeutic index of gene therapy vectors for acute intermittent porphyria. Hum Mol Genet 2018; 27 (21) 3688-3696
    CrossrefPubMedGoogle Scholar
  • 116 Serrano-Mendioroz I, Sampedro A, Alegre M, Enríquez de Salamanca R, Berraondo P, Fontanellas A. An inducible promoter responsive to different porphyrinogenic stimuli improves gene therapy vectors for acute intermittent porphyria. Hum Gene Ther 2018; 29 (04) 480-491
    CrossrefPubMedGoogle Scholar
  • 117 Bustad HJ, Toska K, Schmitt C. et al. A pharmacological chaperone therapy for acute intermittent porphyria. Mol Ther 2020; 28 (02) 677-689
    CrossrefPubMedGoogle Scholar
  • 118 Córdoba KM, Serrano-Mendioroz I, Jericó D. et al. Recombinant porphobilinogen deaminase targeted to the liver corrects enzymopenia in a mouse model of acute intermittent porphyria. Sci Transl Med 2022; 14 (627) eabc0700
    CrossrefPubMedGoogle Scholar
  • 119 Jiang L, Berraondo P, Jericó D. et al. Systemic messenger RNA as an etiological treatment for acute intermittent porphyria. Nat Med 2018; 24 (12) 1899-1909
    CrossrefPubMedGoogle Scholar
  • 120 Russell JO, Monga SP. Wnt/β-catenin signaling in liver development, homeostasis, and pathobiology. Annu Rev Pathol 2018; 13: 351-378
    CrossrefPubMedGoogle Scholar
  • 121 Saggi H, Maitra D, Jiang A. et al. Loss of hepatocyte β-catenin protects mice from experimental porphyria-associated liver injury. J Hepatol 2019; 70 (01) 108-117
    CrossrefPubMedGoogle Scholar
  • 122 Yasuda M, Desnick RJ. Murine models of the human porphyrias: contributions toward understanding disease pathogenesis and the development of new therapies. Mol Genet Metab 2019; 128 (03) 332-341
    CrossrefPubMedGoogle Scholar
  • 123 Sardh E, Harper P, Balwani M. et al. Phase 1 trial of an RNA interference therapy for acute intermittent porphyria. N Engl J Med 2019; 380 (06) 549-558
    CrossrefPubMedGoogle Scholar