Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Acute Intermittent Porphyria Workup

  • Author: Thomas G DeLoughery, MD; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Dec 23, 2015
 

Laboratory Studies

The fundamental step in diagnosing acute intermittent porphyria (AIP) is to demonstrate increased urinary porphobilinogen secretion. If a patient has no increased secretion of porphobilinogen, (ie, a level of 0-4 mg/L during acute symptoms), acute porphyria is eliminated as a cause of the neurovisceral symptoms.[5, 6]

A spot urine test for porphobilinogen can rapidly provide the diagnosis; these tests detect porphobilinogen at levels greater than 6 mg/L. A common error is to order a urine porphyrin screen. Porphobilinogen, a porphyrin precursor, usually is not included in a urine porphyrin screen; it must be ordered specially.

AIP patients have elevated porphobilinogen between attacks. However, in some patients with a remote (years) history of attacks, porphobilinogen can return to the reference range.

Elevation of urine porphyrins, especially coporphobilinogen, is observed. This is caused by spontaneous polymerization of porphobilinogen in the urine. Nonspecific (1-2 times reference range) elevation of urine porphyrins, especially coproporphyrins, is common and is not specific for porphyria. Stool porphyrins are within the reference range or mildly elevated.

Other nonspecific signs in an attack of AIP include the following:

  • Hyponatremia
  • Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
  • Mild leukocytosis

Although a defective enzyme causes AIP, measuring the activity of porphobilinogen deaminase is of little value. Approximately 10% of AIP patients will have normal activity because a different form of the enzyme is expressed in the hematopoietic tissues. The vast majority of patients with the defective enzyme do not have any symptoms of the disease.

Next

Imaging Studies

See the list below:

  • Imaging studies are not helpful.
  • Sometimes, abdomen films demonstrate an ileus.
  • Findings on cranial CT scan are normal.
  • Brain MRI occasionally shows signs of increased edema in patients having very severe attacks.
Previous
Next

Other Tests

Attacks of acute porphyria are clinically indistinguishable in AIP, hereditary coproporphyria, variegate porphyria, and there are few evidence-based diagnostic strategies for these conditions. Whatley et al conducted a retrospective analysis of 467 unrelated patients to determine the diagnostic sensitivity of mutation analysis of the HMBS, CPOX, or PPOX gene.[7] Findings included the following[7] :

  • In the presence of increased porphobilinogen excretion, plasma fluorescence scanning and the coproporphyrin ratio can identify the type of acute porphyria, with rare exceptions.
  • In cases in which the porphobilinogen, 5-aminolevulinate, and porphyrin analyses are within reference intervals and in which the index of suspicion is high of a previous illness caused by an acute porphyria, mutation analysis of the HMBS gene followed by porphobilinogen deaminase assay is an effective strategy for diagnosis or exclusion of AIP.
Previous
 
 
Contributor Information and Disclosures
Author

Thomas G DeLoughery, MD Professor of Medicine, Pathology, and Pediatrics, Divisions of Hematology/Oncology and Laboratory Medicine, Associate Director, Department of Transfusion Medicine, Division of Clinical Pathology, Oregon Health and Science University School of Medicine

Thomas G DeLoughery, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American College of Physicians, American Society of Hematology, International Society on Thrombosis and Haemostasis, Wilderness Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Clarence Sarkodee Adoo, MD, FACP Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program

Clarence Sarkodee Adoo, MD, FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

References
  1. Kuo HC, Huang CC, Chu CC, Lee MJ, Chuang WL, Wu CL, et al. Neurological complications of acute intermittent porphyria. Eur Neurol. 2011. 66(5):247-52. [Medline].

  2. Ramanujam VM, Anderson KE. Porphyria Diagnostics-Part 1: A Brief Overview of the Porphyrias. Curr Protoc Hum Genet. 2015 Jul 1. 86:17.20.1-17.20.26. [Medline].

  3. Cederlöf M, Bergen SE, Larsson H, Landén M, Lichtenstein P. Acute intermittent porphyria: comorbidity and shared familial risks with schizophrenia and bipolar disorder in Sweden. Br J Psychiatry. 2015 Dec. 207 (6):556-7. [Medline].

  4. Bonkovsky HL, Maddukuri VC, Yazici C, Anderson KE, Bissell DM, Bloomer JR, et al. Acute Porphyrias in the USA: Features of 108 Subjects from Porphyria Consortium. Am J Med. 2014 Jul 9. [Medline].

  5. Anyaegbu E, Goodman M, Ahn SY, Thangarajh M, Wong M, Shinawi M. Acute Intermittent Porphyria: A Diagnostic Challenge. J Child Neurol. 2011 Dec 21. [Medline].

  6. Menegueti MG, Gil Cezar AT, Casarini KA, Muniz Cordeiro KS, Basile-Filho A, Martins-Filho OA, et al. Acute intermittent porphyria associated with respiratory failure: a multidisciplinary approach. Crit Care Res Pract. 2011. 2011:283690. [Medline]. [Full Text].

  7. Whatley SD, Mason NG, Woolf JR, et al. 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 Jul. 55(7):1406-14. [Medline].

  8. [Guideline] Stein P, Badminton M, Barth J, Rees D, Stewart MF, British and Irish Porphyria Network. Best practice guidelines on clinical management of acute attacks of porphyria and their complications. Ann Clin Biochem. 2013 May. 50 (Pt 3):217-23. [Medline]. [Full Text].

  9. Pischik E, Kauppinen R. An update of clinical management of acute intermittent porphyria. Appl Clin Genet. 2015. 8:201-14. [Medline]. [Full Text].

  10. Willandt B, Langendonk JG, Biermann K, Meersseman W, D'Heygere F, George C, et al. Liver Fibrosis Associated with Iron Accumulation Due to Long-Term Heme-Arginate Treatment in Acute Intermittent Porphyria: A Case Series. JIMD Rep. 2015 Jun 21. 50 (Pt 3):217-23. [Medline].

  11. Delaby C, To-Figueras J, Deybach JC, et al. Role of two nutritional hepatic markers (insulin-like growth factor 1 and transthyretin) in the clinical assessment and follow-up of acute intermittent porphyria patients. J Intern Med. 2009 Apr 23. epub ahead of print. [Medline].

  12. Syal K, Bhatt R, Singh S, Ohri A. Acute intermittent porphyria. J Anaesthesiol Clin Pharmacol. 2015 Apr-Jun. 31 (2):261-3. [Medline]. [Full Text].

  13. Zaider E, Bickers DR. Clinical laboratory methods for diagnosis of the porphyrias. Clin Dermatol. 1998 Mar-Apr. 16(2):277-93. [Medline].

  14. 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. [Medline].

  15. Bonkovsky HL, Barnard GF. Diagnosis of porphyric syndromes: a practical approach in the era of molecular biology. Semin Liver Dis. 1998. 18(1):57-65. [Medline].

  16. Bylesjo I, Wikberg A, Andersson C. Clinical aspects of acute intermittent porphyria in northern Sweden: A population-based study. Scand J Clin Lab Invest. 2009 Apr 28. 1-7. [Medline].

  17. Daniell WE, Stockbridge HL, Labbe RF, et al. Environmental chemical exposures and disturbances of heme synthesis. Environ Health Perspect. 1997 Feb. 105 Suppl 1:37-53. [Medline].

  18. Elder GH, Smith SG, Smyth SJ. Laboratory investigation of the porphyrias. Ann Clin Biochem. 1990 Sep. 27 ( Pt 5):395-412. [Medline].

  19. Gill R, Kolstoe SE, Mohammed F, et al. Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria. Biochem J. 2009 Apr 28. 420(1):17-25. [Medline].

  20. Gorchein A. Drug treatment in acute porphyria. Br J Clin Pharmacol. 1997 Nov. 44(5):427-34. [Medline].

  21. Hahn M, Bonkovsky HL. Multiple chemical sensitivity syndrome and porphyria. A note of caution and concern. Arch Intern Med. 1997 Feb 10. 157(3):281-5. [Medline].

  22. Kalman DR, Bonkovsky HL. Management of acute attacks in the porphyrias. Clin Dermatol. 1998 Mar-Apr. 16(2):299-306. [Medline].

  23. Kauppinen R, Mustajoki P. Prognosis of acute porphyria: occurrence of acute attacks, precipitating factors, and associated diseases. Medicine (Baltimore). 1992 Jan. 71(1):1-13. [Medline].

  24. Laiwah AC, McColl KE. Management of attacks of acute porphyria. Drugs. 1987 Nov. 34(5):604-16. [Medline].

  25. Massey EW. Neuropsychiatric manifestations of porphyria. J Clin Psychiatry. 1980 Jun. 41(6):208-13. [Medline].

  26. Mattern SE, Tefferi A. Acute porphyria: the cost of suspicion. Am J Med. 1999 Dec. 107(6):621-3. [Medline].

  27. Moore MR. The biochemistry of heme synthesis in porphyria and in the porphyrinurias. Clin Dermatol. 1998 Mar-Apr. 16(2):203-23. [Medline].

  28. Murphy GM. The cutaneous porphyrias: a review. The British Photodermatology Group. Br J Dermatol. 1999 Apr. 140(4):573-81. [Medline].

  29. Peters TJ, Sarkany R. Porphyria for the general physician. Clin Med. 2005 May-Jun. 5(3):275-81. [Medline].

 
Previous
Next
 
Table 1. Drugs Thought Safe in Porphyria*
Acetazolamide acetylcholine



Actinomycin D



Acyclovir



Adenosine monophosphate



Adrenaline



Alclofenac



Allopurinol



Alpha tocopheryl



Acetate



Amethocaine



Amiloride



Aminocaproic acid



Aminoglycosides



Amoxicillin



Amphotericin



Ampicillin



Ascorbic acid



Aspirin



Atenolol



Atropine



Azathioprine



Beclomethasone



Benzhexol HCl



Beta-carotene



Biguanides



[Bromazepam]



Bromides



Buflomedil HCl



Bumetanide



Bupivacaine



Buprenorphine



Buserelin



Butacaine SO4



Canthaxanthin



Carbimazole



[Carpipramine HCl]



Chloral hydrate



[Chlormethiazole]



[Chloroquine]



[Chlorothiazide]



Chlorpheniramine



Chlorpromazine



Ciprofloxacin



Cisapride



Cisplatin



Clavulanic acid



Clofibrate



Clomiphene



Cloxacillin



Co-codamol



Codeine phosphate



Colchicine



[Corticosteroids]



Corticotrophin (adrenocorticotropic hormone [ACTH])



Coumarins



Cyclizine



Cyclopenthiazide



Cyclopropane



[Cyproterone acetate]



Danthron



Desferrioxamine



Dexamethasone



[Dextromoramide]



Dextrose



Diamorphine



Diazoxide



Dicyclomine HCl



Diflunisal



Digoxin



Dihydrocodeine



Dimercaprol



Dimethicone



Dinoprost



Diphenoxylate HCl



Dipyridamole



[Disopyramide]



Domperidone



Doxorubicin HCl



Droperidol



[Estazolam]



Ethacrynic acid



Ethambutol



[Ethinyl oestradiol]



Ethoheptazine citrate



Etoposide



Famotidine



Fenbufen



[Fenofibrate]



Fenoprofen



Fentanyl



Flucytosine



Flumazenil



Fluoxetine HCl



Flurbiprofen



Fluvoxamine



Maleate



Folic acid



Fructose



Fusidic acid



Follicle-stimulating hormone



Gentamicin



Glafenine



Glucagon



Glucose



Glyceryl trinitrate



Goserelin



Guanethidine



Guanfacine HCl



Haem arginate



[Haloperidol]



Heparin



Heptaminol HCl



Hexamine



[Hydrocortisone]



Ibuprofen



Indomethacin



Insulin



Iron



Josamycin



[Ketamine]



Ketoprofen



Ketotifen



Labetalol



Luteinizing hormone–releasing hormone



Liquorice



Lithium



Salts lofepramine



Loperamide



[Lorazepam]



Magnesium-sulphate



[Mebendazole]



Mecamylamine



Meclofenoxate HCl



Meclozine



Mefloquine HCl



[Melphalan]



Meptazinol



Mequitazine



Metformin



Methadone



[Methotrimeprazine]



Methylphenidate



Methyluracil



Metipropranolol



Metopimazine



Metoprolol



[Metronidazole]



[Midazolam]



Minaprine HCl



Minaxolone



Morphine



Nadolol



Naftidrofuryl



Oxalate



[Naproxen sodium]



Natamycin



Nefopam HCl



Neostigmine



Netilmicin



Niflumic acid



Nitrous oxide



Norfloxacin



Ofloxacin



Oxolinic acid



Oxybuprocaine



[Oxyphenbutazone]



Oxytocin



[Pancuronium bromide]



Paracetamol



Paraldehyde



Parapenzolate Br



Penicillamine



Penicillin



Pentolinium



Pericyazine



Pethidine



Phenformin



Phenoperidine



Phentolamine mesylate



Pipotiazine



Palmitate



Piracetam



Pirbuterol



Pirenzepine



Pizotifen



[Prazosin]



[Prednisolone]



Primaquine



Probucol



Procainamide HCl



Procaine



Prochlorperazine



Proguanil HCl



Promazine



Propantheline Br



Propofol



Propranolol



Propylthiouracil



[Proxymetacaine]



Pseudoephedrine HCl



Pyridoxine



[Pyrimethamine]



Quinidine



Quinine



[Ranitidine]



Reserpine



Resorcinol



Salbutamol



Senna



Sodium bromide



Sodium ethylenediaminetetraacetic acid



Sodium fusidate



Sorbitol



Streptomycin



Sulbutiamine



Sulindac



Sulfadoxine



Suxamethonium



Talampicillin



Temazepam



Tetracaine



[Tetracyclines]



Thiouracils



Thyroxine



Tiaprofenic acid



Ticarcillin



Tienilic acid



Timolol maleate



Tolazoline



Tranexamic acid



Triacetyloleandomycin



Triamterene



Triazolam



[Trichlormethiazide]



Trifluoperazine



Trimeprazine



Tartrate



Trimetazidine HCl



Tripelennamine



Tubocurarine



Vancomycin



[Vincristine]



Vitamins



Warfarin sodium



Zidovudine



Zinc Preparations



*Bracketed [] drugs are those in which experimental evidence of porphyrin genicity is conflicting.
Table 2. Drugs Thought Unsafe in Porphyria
Alcuronium



*Alphaxalone



Alphadolone



Alprazolam



Aluminium



Preparations



Amidopyrine



Aminoglutethimide Aminophylline



Amiodarone



*Amitriptyline



[Amphetamines]



*Amylobarbitone



Antipyrine



*Auranofin



*Aurothiomalate



Azapropazone



Baclofen



*Barbiturates



*Bemegride



Bendrofluazide



Benoxaprofen



Benzbromarone



[Benzylthiouracil]



[Bepridil]



Bromocriptine



Busulphan



*Butylscopolamine Captopril



*Carbamazepine



*Carbromal



*Carisoprodol



[Cefuroxime]



[Cephalexin]



[Cephalosporins]



[Cephradine]



[Chlorambucil]



*Chloramphenicol



*Chlordiazepoxide *Chlormezanone



Chloroform



*Chlorpropamide



Cinnarizine



Clemastine



[Clobazam]



[Clomipramine HCl]



[Clonazepam]



Clonidine HCl



*Clorazepate



Cocaine



[Colistin]



Co-trimoxazole



Cyclophosphamide



Cycloserine



Cyclosporin



Danazol



*Dapsone



Dexfenfluramine



Dextropropoxyphene Diazepam



*Dichloralphenazone *Diclofenac Na



Dienoestrol



Diethylpropion



Dihydralazine



*Dihydroergotamine



Diltiazem



*Dimenhydrinate



*Diphenhydramine



[Dothiepin HCl]



Doxycycline



*Dydrogesterone



*Econazole NO3



*Enalapril



Enflurane



*Ergot compounds



Ergometrine maleate Ergotamine tartrate



*Erythromycin



*Estramustine



Ethamsylate



*Ethanol



Ethionamide



*Ethosuximide



*Ethotoin



Etidocaine



Etomidate



Fenfluramine



*Flucloxacillin



*Flufenamic acid



Flunitrazepam



Flupenthixol



Flurazepam



*Frusemide



*Glibenclamide



*Glutethimide



*Glipizide



Gramicidin



*Griseofulvin



[Haloperidol]



*Halothane



*Hydantoins



*Hydralazine



*Hydrochlorothiazide *Hydroxyzine



Hyoscine



*Imipramine



Iproniazid



Isometheptene mucate



[Isoniazid]



Kebuzone



Ketoconazole



*Levonorgestrel



Lignocaine



*Lisinopril



Loprazolam



Loxapine



*Lynestrenol



Lysuride



Maleate



Maprotiline HCl



Mebeverine HCl



*Mecillinam



*Medroxyprogesterone



[Mefenamic acid]



Megestrol acetate



*Mephenytoin



Mepivacaine



*Meprobamate



Mercaptopurine



Mercury compounds



Mestranol



[Metapramine HCl]



Methamphetamine



Methohexitone



Methotrexate



Methoxyflurane



Methsuximide



*Methyldopa



*Methylsulphonal



*Methyprylone



Methysergide



*Metoclopramide



Metyrapone



Mianserin HCl



Miconazole



[Mifepristone]



Minoxidil



*Nandrolone



*Nalidixic acid



Natamycin



*Nandrolone



[Nicergoline]



*Nifedipine



*Nikethamide



Nitrazepam



*Nitrofurantoin



Nordazepam



Norethynodrel



*Norethisterone



[Nortriptyline]



Novobiocin



*Oral contraceptives



*Orphenadrine



Oxanamide



[Oxazepam]



Oxybutynin HCl



Oxycodone



*Oxymetazoline



*Oxyphenbutazone



Oxytetracycline



Paramethadione



Pargyline



*Pentazocine



Perhexiline



Phenacetin



Phenelzine



*Phenobarbitone



Phenoxybenzamine



*Phensuximide



*Phenylbutazone



Phenylhydrazine



*Phenytoin



Pipebuzone



Pipemidic



Acid



Piritramide



*Piroxicam



*Pivampicillin



*Pivmecillinam



Prazepam



Prenylamine



*Prilocaine



*Primidone



[Probenecid]



*Progesterone



Progabide



Promethazine



[Propanidid]



*Pyrazinamide



Pyrrocaine



Quinalbarbitone



Rifampicin



Simvastatin



Sodium aurothiomalate



Sodium oxybate



[Sodium valproate]



*Spironolactone



Stanozolol



Succinimides



*Sulfacetamide



*Sulfadiazine



*Sulfadimidine



*Sulfadoxine



*Sulfamethoxazole *Sulfasalazine



*Sulfonylureas



Sulfinpyrazone



Sulpiride



Sulthiame



Sultopride



*Tamoxifen



*Terfenadine



Tetrazepam



*Theophylline



*Thiopentone Na



Thioridazine



Tilidate



Tinidazole



*Tolazamide



*Tolbutamide



Tranylcypromine



Trazodone HCl



Trimethoprim



[Trimipramine]



Troxidone



Valproate



Valpromide



Veralipride



*Verapamil



*Vibramycin



Viloxazine HCl



[Vinblastine]



[Vincristine]



Zuclopenthixol



*These drugs have been associated with acute attacks of porphyria.



†Bracketed [] drugs are those in which experimental evidence of porphyringenicity is conflicting.



Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.