eMedicine Specialties > Hematology > Heme Synthesis and Disorders

Porphyria, Acute Intermittent: Differential Diagnoses & Workup

Author: Thomas G DeLoughery, MD, Professor of Medicine and Pathology, Divisions of Hematology/Oncology and Laboratory Medicine, Associate Director, Department of Transfusion Medicine, Division of Clinical Pathology, Oregon Health Sciences University
Contributor Information and Disclosures

Updated: Aug 5, 2009

Differential Diagnoses

Abdominal Abscess
Esophagitis
Abdominal Angina
Factitious Disorder
Abdominal Hernias
Fibromyalgia
Acute Mesenteric Ischemia
Gastric Outlet Obstruction
Adrenal Carcinoma
Gastritis, Acute
Adrenal Crisis
Hypertension
Amebic Hepatic Abscesses
Ileus
Aortic Dissection
Intestinal Motility Disorders
Appendicitis
Intestinal Pseudo-obstruction: Surgical Perspective
Bile Duct Strictures
Irritable Bowel Syndrome
Bile Duct Tumors
Lead Nephropathy
Biliary Colic
Mediterranean Fever, Familial
Biliary Disease
Nephrolithiasis
Biliary Obstruction
Nerve Entrapment Syndromes
Biliary Trauma
Ovarian Cysts
Cholecystitis
Pancreatitis, Acute
Choledocholithiasis
Pancreatitis, Chronic
Cholelithiasis
Pelvic Inflammatory Disease
Chronic Pelvic Pain
Porphyria, Chester
Colonic Obstruction
Porphyria, Hereditary Coproporphyria
Constipation
Portal Vein Obstruction
Diverticulitis
Pyelonephritis, Acute
Emphysema
Pyelonephritis, Chronic
Emphysematous Cholecystitis
Toxicity, Lead
Emphysematous Pyelonephritis
Empyema, Gallbladder
Endometriosis

Other Problems to Be Considered

Diverticulosis
Manic-depressive illness

Workup

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, acute porphyria is eliminated as a cause of the neurovisceral symptoms.
    • A common error is the failure to order urine porphyrins. Porphobilinogen, a porphyrin precursor, usually is not included in a urine porphyrin screen and must be ordered specially.
    • AIP patients have elevated porphobilinogen between attacks.
    • 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 indicative of porphyria.
  • Stool porphyrins are within the reference range or mildly elevated.
  • Other nonspecific signs in an attack of AIP include hyponatremia, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and 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.

Imaging Studies

  • 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.

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.1 Findings included the following1 :

  • 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.

More on Porphyria, Acute Intermittent

Overview: Porphyria, Acute Intermittent
Differential Diagnoses & Workup: Porphyria, Acute Intermittent
Treatment & Medication: Porphyria, Acute Intermittent
Follow-up: Porphyria, Acute Intermittent
References
[ CLOSE WINDOW ]

References

  1. 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. Jul 2009;55(7):1406-14. [Medline].

  2. 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. Apr 23 2009;epub ahead of print. [Medline].

  3. Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med. Mar 15 2005;142(6):439-50. [Medline].

  4. 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].

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

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

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

  8. 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. Apr 28 2009;420(1):17-25. [Medline].

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

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

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

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

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

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

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

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

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

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

  19. Poh-Fitzpatrick MB. Clinical features of the porphyrias. Clin Dermatol. Mar-Apr 1998;16(2):251-64. [Medline].

  20. Tefferi A, Colgan JP, Solberg LA Jr. Acute porphyrias: diagnosis and management. Mayo Clin Proc. Oct 1994;69(10):991-5. [Medline].

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

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

acute intermittent porphyria, AIP, defects in heme metabolism, increased secretion of porphobilinogen, abdominal pain, psychiatric problems, hysteria, peripheral neuropathies, abdominal pain, neuropathy, constipation

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Thomas G DeLoughery, MD, Professor of Medicine and Pathology, Divisions of Hematology/Oncology and Laboratory Medicine, Associate Director, Department of Transfusion Medicine, Division of Clinical Pathology, Oregon Health Sciences University
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, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Clarence Sarkodee-Adoo, MD, Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Marcel E Conrad, MD, (Retired) Distinguished Professor of Medicine, University of South Alabama
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, and Southwest Oncology Group
Disclosure: No financial interests None None

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.