Highlights & Basics
- Acute intermittent porphyria (AIP) is a rare autosomal dominant inherited disorder characterized by a partial deficiency of porphobilinogen deaminase, which leads to the accumulation of porphyrin precursors and porphyrins in the body.
- Most individuals remain asymptomatic, but symptoms can be triggered by use of certain drugs, steroid hormones, or alteration of nutritional status.
- The most common presenting features include pain in the abdomen, extremities, back, and chest, tachycardia, hypertension, nausea, vomiting, constipation, and peripheral motor neuropathy.
- The pain is neuropathic and not accompanied by inflammation.
- Red or brownish urine results from marked increases in urinary excretion of heme pathway intermediates. Porphyrins are reddish and fluoresce when exposed to long-wave ultraviolet light. Porphobilinogen is colorless but degrades on standing to form porphyrins and brownish pigments.
Quick Reference
History & Exam
Key Factors
Other Factors
Diagnostics Tests
Treatment Options
Definition
Epidemiology
Etiology
Pathophysiology
Citations
Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. N Engl J Med. 2017 Aug 31;377(9):862-72. [Abstract]
Phillips JD, Anderson KE. The porphyrias (Chapter 59). In: Kaushansky K, Lichtman MA, Prchal JT, et al, eds. Williams Hematology, 10th edition. McGraw-Hill, 2021: 961-86.
Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med. 2005 Mar 15;142(6):439-50.[Abstract]
American Porphyria Foundation. Emergency room guidelines for acute porphyrias [internet publication].[Full Text]
1. Pischik E, Kauppinen R. An update of clinical management of acute intermittent porphyria. Appl Clin Genet. 2015;8:201-14.[Abstract][Full Text]
2. 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 Nov;37(11):1215-22.[Abstract][Full Text]
3. Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. N Engl J Med. 2017 Aug 31;377(9):862-72. [Abstract]
4. Phillips JD, Anderson KE. The porphyrias (Chapter 59). In: Kaushansky K, Lichtman MA, Prchal JT, et al, eds. Williams Hematology, 10th edition. McGraw-Hill, 2021: 961-86.
5. Gerischer LM, Scheibe F, Nümann A, et al. Acute porphyrias - a neurological perspective. Brain Behav. 2021 Nov;11(11):e2389.[Abstract][Full Text]
6. Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med. 2005 Mar 15;142(6):439-50.[Abstract]
7. Yasuda M, Chen B, Desnick RJ. Recent advances on porphyria genetics: inheritance, penetrance & molecular heterogeneity, including new modifying/causative genes. Mol Genet Metab. 2019 Nov;128(3):320-31.[Abstract][Full Text]
8. Grandchamp B, Picat C, Mignotte V, et al. Tissue-specific splicing mutation in acute intermittent porphyria. Proc Natl Acad Sci USA. 1989 Jan;86(2):661-4.[Abstract][Full Text]
9. 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 Feb;43(1):1-26.[Abstract][Full Text]
10. Anderson KE, Spitz IM, Bardin CW, et al. A GnRH analogue prevents cyclical attacks of porphyria. Arch Int Med. 1990 Jul;150(7):1469-74.[Abstract]
11. Welland FH, Hellman ES, Gaddis EM, et al. Factors affecting the excretion of porphyrin precursors by patients with acute intermittent porphyria. 1. The effect of diet. Metabolism. 1964 Mar;13:232-50.[Abstract]
12. Bonkowsky HL, Collins A, Doherty JM, et al. The glucose effect in rat liver: studies of δ-aminolevulinate synthetase and tyrosine aminotransferase. Biochim Biophys Acta. 1973 Oct 5;320(3):561-75.[Abstract]
13. Handschin C, Lin J, Rhee J, et al. Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-1alpha. Cell. 2005 Aug 26;122(4):505-15.[Abstract][Full Text]
14. Lip GYH, McColl KEL, Goldberg A, et al. Smoking and recurrent attacks of acute intermittent porphyria. Br Med J. 1991 Mar 2;302(6775):507.[Abstract][Full Text]
15. Bonkovsky HL, Maddukuri VC, Yazici C, et al. Acute porphyrias in the USA: features of 108 subjects from Porphyrias Consortium. Am J Med. 2014 Dec;127(12):1233-41.[Abstract][Full Text]
16. Wang B, Bonkovsky HL, Lim JK, et al. AGA clinical practice update on diagnosis and management of acute hepatic porphyrias: expert review. Gastroenterology. 2023 Mar;164(3):484-91.[Abstract][Full Text]
17. American College of Medical Genetics and Genomics. Five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication].[Full Text]
18. Blake D, McManus J, Cronin V, et al. Fecal coproporphyrin isomers in hereditary coproporphyria. Clin Chem. 1992 Jan;38(1):96-100.[Abstract]
19. Kühnel A, Gross U, Jacob K, et al. Studies on coproporphyrin isomers in urine and feces in the porphyrias. Clin Chim Acta. 1999 Apr;282(1-2):45-58.[Abstract]
20. Anderson KE, Sassa S, Peterson CM, et al. Increased erythrocyte uroporphyrinogen-I-synthetase, γ-aminolevulinic acid dehydratase and protoporphyrin in hemolytic anemias. Am J Med. 1977 Sep;63(3):359-64.[Abstract]
21. Akagi R, Kato N, Inoue R, et al. delta-Aminolevulinate dehydratase (ALAD) porphyria: the first case in North America with two novel ALAD mutations. Mol Genet Metab. 2006 Apr;87(4):329-36.[Abstract]
22. Poh-Fitzpatrick MB. A plasma porphyrin fluorescence marker for variegate porphyria. Arch Dermatol. 1980 May;116(5):543-7.[Abstract]
23. Hift RJ, Davidson BP, Van der Hooft C, et al. Plasma fluorescence scanning and fecal porphyrin analysis for the diagnosis of variegate porphyria: precise determination of sensitivity and specificity with detection of protoporphyrinogen oxidase mutations as a reference standard. Clin Chem. 2004 May;50(5):915-23. [Abstract][Full Text]
24. American Porphyria Foundation. Emergency room guidelines for acute porphyrias [internet publication].[Full Text]
25. American Porphyria Foundation. Diagnosis of the porphyrias [internet publication].[Full Text]
26. Balwani M, Wang B, Anderson KE, et al. Acute hepatic porphyrias: recommendations for evaluation and long-term management. Hepatology. 2017 Oct;66(4):1314-22.[Abstract][Full Text]
27. Anderson KE, Bonkovsky HL, Bloomer JR, et al. Reconstitution of hematin for intravenous infusion. Ann Intern Med. 2006 Apr 4;144(7):537-8.[Abstract]
28. Ventura P, Bonkovsky HL, Gouya L, et al. Efficacy and safety of givosiran for acute hepatic porphyria: 24-month interim analysis of the randomized phase 3 ENVISION study. Liver Int. 2022 Jan;42(1):161-72.[Abstract][Full Text]
29. 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 Mar 12;22:57-65.[Abstract][Full Text]
30. 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 Feb 21;36:99-107.[Abstract][Full Text]
31. Soonawalla ZF, Orug T, Badminton MN, et al. Liver transplantation as a cure for acute intermittent porphyria. Lancet. 2004 Feb 28;363(9410):705-6.[Abstract]
32. Seth AK, Badminton MN, Mirza D, et al. Liver transplantation for porphyria: who, when, and how? Liver Transpl. 2007 Sep;13(9):1219-27.[Abstract][Full Text]
33. Dowman JK, Gunson BK, Mirza DF, et al. Liver transplantation for acute intermittent porphyria is complicated by a high rate of hepatic artery thrombosis. Liver Transpl. 2012 Feb;18(2):195-200.[Abstract][Full Text]
34. Lissing M, Nowak G, Adam R, et al. Liver transplantation for acute intermittent porphyria. Liver Transpl. 2021 Apr;27(4):491-501.[Abstract][Full Text]
35. 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 Oct;65(4):776-83.[Abstract][Full Text]
36. Jeans JB, Savik K, Gross CR, et al. Mortality in patients with acute intermittent porphyria requiring hospitalization: a United States case series. Am J Med Genet. 1996 Nov 11;65(4):269-73.[Abstract]
37. Church SE, McColl KE, Moore MR, et al. Hypertension and renal impairment as complications of acute porphyria. Nephrol Dial Transplant. 1992;7(10):986-90.[Abstract]
38. Pallet N, Mami I, Schmitt C, et al. High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria. Kidney Int. 2015 Aug;88(2):386-95.[Abstract][Full Text]
39. 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 Jun;28(6):1924-32.[Abstract][Full Text]
40. Sardh E, Andersson DE, 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 Feb 16;55(1):66-71.[Abstract]
41. Nunez DJ, Williams PF, Herrick AL, et al. Renal transplantation for chronic renal failure in acute porphyria. Nephrol Dial Transplant. 1987;2(4):271-4.[Abstract]
42. Wahlin S, Harper P, Sardh E, et al. Combined liver and kidney transplantation in acute intermittent porphyria. Transpl Int. 2010 Jun;23(6):e18-21.[Abstract][Full Text]
43. Sardh E, Wahlin S, Björnstedt M, et al. High risk of primary liver cancer in a cohort of 179 patients with acute hepatic porphyria. J Inherit Metab Dis. 2013 Nov;36(6):1063-71.[Abstract]
44. Andant C, Puy H, Bogard C, et al. Hepatocellular carcinoma in patients with acute hepatic porphyria: frequency of occurrence and related factors. J Hepatol. 2000 Jun;32(6):933-9.[Abstract]
