Management and prognosis of acute intermittent porphyria
- Gagan K Sood, MD
Gagan K Sood, MD
- Associate Professor, Department of Surgery and Medicine
- Baylor College of Medicine
- Karl E Anderson, MD, FACP
Karl E Anderson, MD, FACP
- The University of Texas Medical Branch
- Section Editors
- Donald H Mahoney, Jr, MD
Donald H Mahoney, Jr, MD
- Section Editor — Pediatric Hematology
- Professor of Pediatrics
- Baylor College of Medicine
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Blood Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
Acute intermittent porphyria (AIP, Swedish porphyria, pyrroloporphyria, intermittent acute porphyria) is an autosomal dominant disorder of low penetrance resulting from a partial deficiency of porphobilinogen deaminase (PBGD, hydroxymethylbilane synthase [HMBS], previously called uroporphyrinogen I synthase), the third enzyme in the heme biosynthetic pathway (figure 1 and figure 2). Symptoms in AIP are due to effects on the visceral, peripheral, autonomic, and central nervous systems. They usually occur as intermittent attacks that are sometimes life-threatening due to neurologic complications (eg, seizures, paralysis).
The management of patients with attacks of AIP can be challenging because the disease manifestations are diverse and potentially life-threatening. Timely intervention can resolve and prevent attacks, and close long-term monitoring for complications is needed. Further, it is important not only to treat the porphyria, but also to address any other condition (eg, infection, medication exposure) that may have triggered the acute attack.
The management of AIP is reviewed here, including treatment of acute attacks, prevention, and long-term monitoring for complications. The clinical manifestations and diagnosis of AIP and a general overview of the porphyrias are presented separately. (See "Pathogenesis, clinical manifestations, and diagnosis of acute intermittent porphyria" and "Porphyrias: An overview".)
TESTING BEFORE THERAPY
Demonstration of an elevation of urinary porphobilinogen (PBG) remains central to the diagnosis of acute porphyria. This finding is specific for the three most common acute porphyrias. Substantial PBG elevation (which occurs only in AIP, hereditary coproporphyria [HCP], and variegate porphyria [VP]) should be established, or have been established in the past, before treatment is started, particularly with hemin. However, therapy for an acute attack does not require differentiation among these types of porphyria. The diagnosis of an attack in a patient with known acute porphyria is primarily clinical.
For patients who require further diagnostic testing to determine the type of porphyria, samples should be obtained prior to initiating therapy if possible, but determination of the specific type of porphyria should not delay therapy. A prior diagnosis of AIP or other acute porphyria cannot be assumed to be correct. Therefore, the evidence for the prior diagnosis should be available for review. If this is not available, a spot urine should be obtained and tested for PBG as soon as possible. Once it is known that an acute porphyria is indeed present, individual attacks are diagnosed and treated based on clinical findings (eg, typical symptoms), although confirmation of PBG elevation with each attack is recommended.
- Floderus Y, Sardh E, Möller C, et al. Variations in porphobilinogen and 5-aminolevulinic acid concentrations in plasma and urine from asymptomatic carriers of the acute intermittent porphyria gene with increased porphyrin precursor excretion. Clin Chem 2006; 52:701.
- Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005; 142:439.
- Deacon AC, Peters TJ. Identification of acute porphyria: evaluation of a commercial screening test for urinary porphobilinogen. Ann Clin Biochem 1998; 35 ( Pt 6):726.
- Bonkowsky HL, Sinclair PR, Emery S, Sinclair JF. Seizure management in acute hepatic porphyria: risks of valproate and clonazepam. Neurology 1980; 30:588.
- Larson AW, Wasserstrom WR, Felsher BF, Chih JC. Posttraumatic epilepsy and acute intermittent porphyria: effects of phenytoin, carbamazepine, and clonazepam. Neurology 1978; 28:824.
- Bonkowsky HL, Tschudy DP. Letter: Hazard of propranolol in treatment of acute prophyria. Br Med J 1974; 4:47.
- Harper P, Wahlin S. Treatment options in acute porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria. Curr Treat Options Gastroenterol 2007; 10:444.
- Mustajoki P, Nordmann Y. Early administration of heme arginate for acute porphyric attacks. Arch Intern Med 1993; 153:2004.
- Tenhunen R, Mustajoki P. Acute porphyria: treatment with heme. Semin Liver Dis 1998; 18:53.
- http://bdipharma.com/Product%20Inserts/Ovation/panhematin_pi.pdf (Accessed on June 27, 2014).
- Green D, Reynolds N, Klein J, et al. The inactivation of hemostatic factors by hematin. J Lab Clin Med 1983; 102:361.
- Jones RL. Hematin-derived anticoagulant. Generation in vitro and in vivo. J Exp Med 1986; 163:724.
- Bonkovsky HL, Healey JF, Lourie AN, Gerron GG. Intravenous heme-albumin in acute intermittent porphyria: evidence for repletion of hepatic hemoproteins and regulatory heme pools. Am J Gastroenterol 1991; 86:1050.
- Anderson KE, Bonkovsky HL, Bloomer JR, Shedlofsky SI. Reconstitution of hematin for intravenous infusion. Ann Intern Med 2006; 144:537.
- Sood G, Anderson KE. Porphyrias. In: Evidence-Based Hematology, Crowther MA, Ginsberg J, Schunemann H, et al (Eds), Wiley, Hoboken 2008.
- Herrick AL, McColl KE, Moore MR, et al. Controlled trial of haem arginate in acute hepatic porphyria. Lancet 1989; 1:1295.
- 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; 65:269.
- Daimon M, Susa S, Igarashi M, et al. Administration of heme arginate, but not hematin, caused anaphylactic shock. Am J Med 2001; 110:240.
- Khanderia U. Circulatory collapse associated with hemin therapy for acute intermittent porphyria. Clin Pharm 1986; 5:690.
- Dhar GJ, Bossenmaier I, Cardinal R, et al. Transitory renal failure following rapid administration of a relatively large amount of hematin in a patient with acute intermittent porphyria in clinical remission. Acta Med Scand 1978; 203:437.
- Frei P, Minder EI, Corti N, et al. Liver Transplantation because of Acute Liver Failure due to Heme Arginate Overdose in a Patient with Acute Intermittent Porphyria. Case Rep Gastroenterol 2012; 6:190.
- Marcus DL, Nadel H, Lew G, Freedman ML. Cimetidine suppresses chemically induced experimental hepatic porphyria. Am J Med Sci 1990; 300:214.
- Cherem JH, Malagon J, Nellen H. Cimetidine and acute intermittent porphyria. Ann Intern Med 2005; 143:694.
- Prabahar MR, Manorajan R, Sathiyakumar D, et al. Hemodialysis: a therapeutic option for severe attacks of acute intermittent porphyria in developing countries. Hemodial Int 2008; 12:34.
- Schwartz J, Padmanabhan A, Aqui N, et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue. J Clin Apher 2016; 31:149.
- Available from the American Porphyria Foundation at www.porphyriafoundation.com (Accessed on January 21, 2010).
- Available from the European Porphyria Initiative at www.porphyria-europe.com (Accessed on January 21, 2010).
- Bonkovsky HL, Siao P, Roig Z, et al. 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.
- Anderson KE, Spitz IM, Bardin CW, Kappas A. A gonadotropin releasing hormone analogue prevents cyclical attacks of porphyria. Arch Intern Med 1990; 150:1469.
- De Block CE, Leeuw IH, Gaal LF. Premenstrual attacks of acute intermittent porphyria: hormonal and metabolic aspects - a case report. Eur J Endocrinol 1999; 141:50.
- Yamamori I, Asai M, Tanaka F, et al. Prevention of premenstrual exacerbation of hereditary coproporphyria by gonadotropin-releasing hormone analogue. Intern Med 1999; 38:365.
- Anderson KE, Egger NG, Goeger DE. Heme arginate for prevention of acute porphyric attacks (abstract). Acta Haematol 1997; 98, Suppl 1:120.
- Stewart MF. Review of hepatocellular cancer, hypertension and renal impairment as late complications of acute porphyria and recommendations for patient follow-up. J Clin Pathol 2012; 65:976.
- Innala E, Andersson C. Screening for hepatocellular carcinoma in acute intermittent porphyria: a 15-year follow-up in northern Sweden. J Intern Med 2011; 269:538.
- Badminton MN, Deybach JC. Treatment of an acute attack of porphyria during pregnancy. Eur J Neurol 2006; 13:668.
- Soonawalla ZF, Orug T, Badminton MN, et al. Liver transplantation as a cure for acute intermittent porphyria. Lancet 2004; 363:705.
- Seth AK, Badminton MN, Mirza D, et al. Liver transplantation for porphyria: who, when, and how? Liver Transpl 2007; 13:1219.
- TESTING BEFORE THERAPY
- Confirm acute porphyria
- Establish presence of an acute attack
- THERAPY FOR AN ACUTE ATTACK
- Overview of therapy
- Paresis and paralysis
- Treatment of other symptoms
- Intravenous hemin
- Carbohydrate loading
- Elimination of exacerbating factors
- Other treatments
- THERAPY FOR SUBACUTE OR CHRONIC SYMPTOMS
- PREVENTION OF ATTACKS
- MONITORING FOR COMPLICATIONS OF DISEASE AND THERAPY
- LIVER TRANSPLANTATION
- GENETIC COUNSELING
- SUMMARY AND RECOMMENDATIONS