Acute Hepatic Porphyrias in Colombia: An Analysis of 101 Patients

  • Daniel A. Jaramillo-CalleEmail author
  • Daniel C. Aguirre Acevedo
Research Report
Part of the JIMD Reports book series (JIMD, volume 44)


Background: There is minimal information available about acute hepatic porphyrias (AHPs) in developing countries. The aim of this study was to describe the demographics, clinical features, and mortality of AHPs in Colombia.

Patients and methods: 121 patients with presumed diagnosis of AHPs were reported in Colombia between 1944 and 2018. A pooled analysis of 53 patients with confirmed diagnosis was performed to evaluate the demographics, clinical features, and mortality of AHPs in the country. Selected variables were compared by periods (1952–2000 and 2001–2018).

Results: Most attacks occurred in women (66%), with a women-to-man ratio of 39/14. 96% of the patients were diagnosed with AHPs between 15 and 40 years of age. Precipitants were identified in 71% of attacks and more than one precipitant in 41% of them. Drugs (85%) and infections (44%) were the most common precipitants. 11% of women had premenstrual attacks. Abdominal pain was the most common symptom (96%). Cortical blindness, posterior reversible encephalopathy syndrome, and rhabdomyolysis were described. 70% of attacks were confirmed by qualitative test only. 67% of attacks were treated with intravenous heme. The use of heme increased from 4 to 85% in the last two decades. Mortality decreased about twofold in relation to the increase in the use of heme. Severe motor neuropathy was associated with increased mortality. Gonadorelin analogues, heme prophylaxis, and orthotopic liver transplantation have been used to prevent recurrent attacks.

Conclusions: Diagnosis and treatment of AHPs in Colombia have improved in recent decades. However, there are still important shortcomings to address.


Colombia Developing countries Diagnostic errors Hematin Heme Latin America Mortality Porphyria Rare diseases 



Acute hepatic porphyrias


Acute intermittent porphyria


Aminolevulinic acid


Aminolevulinic acid synthase 1


Deoxyribonucleic acid


Gonadorelin analogs


Hereditary coproporphyria


Hydroxymethylbilane synthase


Norwegian Porphyria Centre


Orthotopic liver transplantation




Posterior reversible encephalopathy syndrome


Ribonucleic acid


Variegate porphyria



We thank Jesenia Avendaño and Luis C. Hoyos for helping us obtain the articles.

Supplementary material

477624_1_En_125_MOESM1_ESM.doc (66 kb)
Supplementary Material (DOC 65 kb)


  1. Aarsand AK, Villanger JH, Støle E et al (2011) European specialist porphyria laboratories: diagnostic strategies, analytical quality, clinical interpretation, and reporting as assessed by an external quality assurance program. Clin Chem 57:1514–1523CrossRefGoogle Scholar
  2. Adams CD, Amaya PF (2014) Quadriparesis and rhabdomyolysis due to acute intermittent porphyria: case report. Acta Med Colomb 39:28Google Scholar
  3. Andersson C, Innala E, Bäckström T (2003) Acute intermittent porphyria in women: clinical expression, use and experience of exogenous sex hormones. A population-based study in Northern Sweden. J Intern Med 254:176–183CrossRefGoogle Scholar
  4. Angel DI, Siza LM, Fonseca DJ et al (2010) Acute intermittent porphyria (AIP) identification by sequencing a mutation not previously reported, in patient from the city of Bogotá. Iatreia 23:4SGoogle Scholar
  5. Argüello M, Vergara I, Mora MC et al (1978) Acute intermittent porphyia study of 23 cases. Acta Med Colomb 3:217–239Google Scholar
  6. Balwani M, Wang B, Anderson K et al (2017) Acute hepatic porphyrias: recommendations for evaluation and long term management. Hepatology 66:1314–1322CrossRefGoogle Scholar
  7. Bhat JI, Qureeshi UA, Bhat MA (2010) Acute intermittent porphyria with transient cortical blindness. Indian Pediatr 47:977–978CrossRefGoogle Scholar
  8. Bissell DM, Anderson KE, Bonkovsky HL (2017) Porphyria. N Engl J Med 377:862–872CrossRefGoogle Scholar
  9. Bonkovsky HL, Maddukuri VC, Yazici C et al (2014) Acute hepatic porphyrias in the USA: features of 108 subjects from porphyrias consortium. Am J Med 127:1233–1241CrossRefGoogle Scholar
  10. Buitrago J, Santa SV (2009) Acute intermittent porphyria presenting as spontaneous hemothorax. Biomedica 29:339–347CrossRefGoogle Scholar
  11. Bylesjö I, Wikberg A, Andersson C (2009) Clinical aspects of acute intermittent porphyria in northern sweden: a population-based study. Scand J Clin Lab Invest 69:612–618CrossRefGoogle Scholar
  12. Chen MC, Chang CJ, Lu YH et al (2015) R173W mutation of hydroxymethylbilane synthetase is associated with acute intermittent porphyria complicated with rhabdomyolysis. J Clin Gastroenterol 49:256–257CrossRefGoogle Scholar
  13. Chen B, Solis-Villa C, Erwin A et al (2018) Identification and characterization of 40 novel hydroxymethylbilane synthase mutations that cause acute intermittent porphyria. J Inherit Metab Dis.
  14. Contreras-Zúñiga E, Zuluaga-Martínez SX (2006) Porphyria and pregnancy: a case report Eduardo. Rev Colomb Obstet Ginecol 57:216–218Google Scholar
  15. D’Avola D, López-franco E, Sangro B et al (2016) Phase I open label liver-directed gene therapy clinical trial for acute intermittent porphyria. J Hepatol 65:776–783CrossRefGoogle Scholar
  16. Deacon AC, Elder GH (2011) ACP Best Practice No 165: front line tests for the investigation of suspected porphyria. J Clin Pathol. 54:500–507CrossRefGoogle Scholar
  17. De Siervi A, Rossetti MV, Parera VE et al (1999) Acute intermittent porphyria:biochemical and clinical analysis in the argentinean population. Clin Chim Acta 288:263–271CrossRefGoogle Scholar
  18. Devars du Mayne JF, Deybach JC, Nordmann Y et al (1987) Rhabdomyolysis in acute intermittent porphyria. Presse Med 16:310PubMedGoogle Scholar
  19. Doss MO (1987) Porphyrinurias and occupational disease. Ann N Y Acad Sci 514:204–218CrossRefGoogle Scholar
  20. Enríquez-marulanda A, Shinchi M, Granados AM et al (2016) Acute intermittent porphyria and it’s relationship with posterior reversible encephalopathy syndrome: case report. Acta Neurol Colomb 32:155–160CrossRefGoogle Scholar
  21. García-Martul M, Santana-Cabrera L, Santos-Moyano Z et al (2008) Rhabdomyolysis after correction of severe to an attack of acute intermittent porphyria. Nefrologia 28:563–564PubMedGoogle Scholar
  22. Garg MK, Mohapatro AK, Dugal JS et al (1999) Cortical blindness in acute intermittent porphyria. J Assoc Physicians India 47:727–729PubMedGoogle Scholar
  23. Hift RJ, Meissner PN (2005) An analysis of 112 acute porphyric attacks in Cape Town, South Africa. Medicine (Baltimore) 84:48–60CrossRefGoogle Scholar
  24. Innala E, Bäckström T, Bixo M (2010) Evaluation of gonadotropin-releasing hormone agonist treatment for prevention of menstrual-related attacks in acute porphyria. Acta Obstet Gynecol Scand 89(1):95–100CrossRefGoogle Scholar
  25. Jaramillo-Calle DA (2017) Porphyria. N Engl J Med 377:2100–2101CrossRefGoogle Scholar
  26. Jaramillo-Calle DA, Castaño O, Marín JI et al (2018) Is liver transplantation for intractable attacks of porphyria a viable treatment in a developing country? Hepatology 67:802–803CrossRefGoogle Scholar
  27. Jeans JB, Savik K, Gross CR (1996) Mortality in patients with acute intermittent porphyria requiring hospitalization: a United States case series. Am J Med Genet 65:269–273CrossRefGoogle Scholar
  28. Kauppinen R, Mustajoki P (1992) Prognosis of acute porphyria:occurrence of acute attacks, precipitating factors, and associated diseases. Medicine (Baltimore) 71:1–13CrossRefGoogle Scholar
  29. Kupferschmidt H, Bont A, Schnorf H et al (1995) Transient cortical blindness and bioccipital brain lesions in two patients with acute intermittent porphyria. Ann Intern Med 123:598–600CrossRefGoogle Scholar
  30. Latorre G, Muñoz A (1988) Acute intermittent porphyria University Hospital San Vicente de Paul (1974-1987). Acta Med Colomb 13:443–451Google Scholar
  31. Leung-Pineda V, Wilson DP (2017) Severe abdominal pain with hyponatremia. Clin Chem 63(9):1544–1554CrossRefGoogle Scholar
  32. Marsden JT, Peters TJ (2004) Rhabdomyolysis in a patient with acute intermittent porphyria. Ann Clin Biochem 41:341–343CrossRefGoogle Scholar
  33. Marsden JT, Rees DC (2010) A retrospective analysis of outcome of pregnancy in patients with acute porphyria. J Inherit Metab Dis 33:591–596CrossRefGoogle Scholar
  34. Marsden JT, Guppy S, Stein P et al (2015) Audit of the use of regular haem arginate infusions in patients with acute porphyria to prevent recurrent symptoms. JIMD Rep 22:57–65CrossRefGoogle Scholar
  35. Mendoza F, Pareja J, Zambrano R (1995) Hepatic porphyria with neurological manifestations. Acta Med Colomb 20:248–250Google Scholar
  36. Mustajoki P, Koskelo P (1976) Hereditary hepatic porphyrias in Finland. Acta Med Scand 200:171–178CrossRefGoogle Scholar
  37. Mustajoki P, Nordmann Y (1993) Early administration of heme arginate for acute porphyric attacks. Arch Intern Med 153:2004–2008CrossRefGoogle Scholar
  38. Mykletun M, Aasne AK, Støle E et al (2014) Porphyrias in Norway. Tidsskr Nor Laegeforen 134:831–836CrossRefGoogle Scholar
  39. Olivier P, Van Melkebeke D, Honoré PJ et al (2017) Cerebral vasospasm in acute porphyria. Eur J Neurol 24:1183–1187CrossRefGoogle Scholar
  40. Ordoñez JH (1944) Acute porphyrinosis (clinical and electrocardiographic study). Anal Soc Biol Bogota 1:132–144Google Scholar
  41. Pischik E, Bulyanitsa A, Kazakov V et al (2004) Clinical features predictive of a poor prognosis in acute porphyria. J Neurol 251:1538–1541CrossRefGoogle Scholar
  42. Pradilla G, Acevedo A, Martínez P (1980) Acute intermittent porphyria. Therapeutic advances in propanolol and hematin. Acta Neurol Colomb 5:642–651Google Scholar
  43. Ramírez J (1959) Acute porphyria and pregnancy (topic review and case presentation). Rev Colomb Obstet Ginecol 10:428–441Google Scholar
  44. Sardh E, Harper P, Al-Tawil N et al (2016) Interim data from a randomized, placebo controlled, phase 1 study of Aln-AS1, an investigational RNAi therapeutic for the treatment of acute hepatic porphyria. Blood 128:2318Google Scholar
  45. Sardh E, Gouya L, Bloomer J et al (2017) Explore: a prospective, multinational natural history study of patients with acute hepatic porphyrias with recurrent attacks. Blood 130:2211Google Scholar
  46. Schmitt C, Lenglet H, Yu A et al (2018) Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver. J Intern Med. CrossRefGoogle Scholar
  47. Schulenburg-Brand D, Gardiner T, Guppy S et al (2017) An audit of the use of gonadorelin analogues to prevent recurrent acute symptoms in patients with acute porphyria in the United Kingdom. JIMD Rep 36:99–107CrossRefGoogle Scholar
  48. Soonawalla ZF, Orug T, Badminton MN et al (2004) Liver transplantation as a cure for acute intermittent porphyria. Lancet 363:705–706CrossRefGoogle Scholar
  49. Stein JA, Tschudy DP (1970) Acute intermittent porphyria. A clinical and biochemical study of 46 patients. Medicine (Baltimore) 49:1–16CrossRefGoogle Scholar
  50. Stein P, Badminton M, Barth J et al (2013) Best practice guidelines on clinical management of acute attacks of porphyria and their complications. Ann Clin Biochem 50:217–223CrossRefGoogle Scholar
  51. Uribe CU, Perez A, Guerra A et al (2007) Reversible angioespasm in acute intermittent porphyria and persistence of severe leukoencephalopathy. Acta Neurol Colomb 23:188Google Scholar
  52. Whatley SD, Mason NG, Woolf JR et al (2009) Diagnostic strategies for autosomal dominant acute hepatic porphyrias: retrospective analysis of 467 unrelated patients referred for mutational analysis of the HMBS, CPOX, or PPOX gene. Clin Chem 55:1406–1414CrossRefGoogle Scholar
  53. Willandt B, Langendonk JG, Biermann K et al (2015) Liver fibrosis associated with iron accumulation due to long-term heme-arginate treatment in acute intermittent porphyria: a case series. JIMD Rep 25:77–81CrossRefGoogle Scholar
  54. Woolf J, Marsden JT, Degg T et al (2017) Best practice guidelines on first-line laboratory testing for porphyria. Ann Clin Biochem 54:188–198CrossRefGoogle Scholar
  55. Yasuda M, Bishop DF, Fowkes M et al (2010) AAV8-mediated gene therapy prevents induced biochemical attacks of acute intermittent porphyria and improves neuromotor function. Mol Ther 18:17–22CrossRefGoogle Scholar
  56. Yrjönen A, Pischik E, Mehtälä S et al (2008) A novel 19-Bp deletion of exon 15 in the HMBS gene causing acute intermittent porphyria associating with rhabdomyolysis during an acute attack. Clin Genet 74:396–398CrossRefGoogle Scholar

Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Daniel A. Jaramillo-Calle
    • 1
    Email author
  • Daniel C. Aguirre Acevedo
    • 2
  1. 1.Colombian Porphyria Research Group (PorfiCol)IPS Universitaria – Universidad de AntioquiaMedellínColombia
  2. 2.Institute of Medical Research, Universidad de AntioquiaMedellínColombia

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