Porphyrin Tests: Ask Us

At a Glance

Why Get Tested?

To help diagnose and sometimes to monitor porphyrias

When to Get Tested?

When a patient has symptoms that suggest an acute neurologic/psychiatric porphyria, such as abdominal pain, tingling in hands or feet, and/or confusion or hallucinations, or that suggest a cutaneous porphyria, such as reddening, blistering, or scarring on sun-exposed skin

Sample Required?

A blood sample drawn from a vein in your arm, a random or 24-hour urine sample, and/or a stool sample

Test Preparation Needed?

None

The Test Sample

What is being tested?

Porphyrins are a group of compounds defined by their chemical structure. They are an integral part of certain proteins found in the body such as hemoglobin, myoglobin, and specific enzymes. Porphyrin tests are assays that are used to help diagnose and monitor a group of disorders called porphyrias. Most porphyrin tests detect and measure the by-products of heme synthesis. Heme, an iron-containing pigment, is a part of hemoglobin and a number of other proteins. The synthesis of heme is a step-by-step process that requires the sequential action of eight different enzymes. If there is a deficiency in one of these enzymes, a bottleneck forms and precursors (porphyrins such as uroporphyrins, coproporhyrins, and protoporhyrins) build up in the bodys fluids and tissues and are excreted in urine and feces. The precursors that build up depend on where the bottleneck (or enzyme deficiency) is located.

There are six major porphyrias, and each one is associated with a different enzyme deficiency. Most porphyrias are inherited in an autosomal dominant fashion, with one normal and one affected gene. This results in about a 50% reduction in the activity of the heme-related enzyme. Enough heme is synthesized to prevent the affected person from becoming anemic, but a large excess of one or more precursors is produced.

Porphyrias may be classified according to:

The affected enzyme
The part of the body where the excess porphyrins are produced
- Hepatic - associated with the liver
- Erythropoietic - associated with red blood cell production or
The signs and symptoms of the disease (neurological/psychiatric, cutaneous, or both).

Those porphyrias that cause neurological/psychiatric symptoms present with acute attacks that may last for days or weeks. They are associated with abdominal pain, nausea, constipation, depression, confusion, hallucinations, and seizures. Attacks may be triggered by a variety of drugs (such as anticonvulsants, antibiotics, and hormones) and environmental factors (such as dietary changes, stress, and exposure to toxic substances).

The cutaneous porphyrias are associated with photosensitivity. Sunlight exposure, even through a glass window, has a toxic effect on the patients skin. This may cause redness, swelling, and a burning sensation in some patients, while in others it leads to blistering, skin thickening, hyperpigmentation, and in some cases scarring.

Acute attack porphyrias (neurological/psychiatric) include:

Acute intermittent porphyria (AIP), the most common of the neurological porphyrias
Variegate porphyria (VP), which includes both neurological symptoms and photosensitivity
Hereditary coproporphyria (HCP), which may present with neurological symptoms, photosensitivity, or both

Cutaneous porphyrias include:

Porphyria cutanea tarda (PCT), the most common porphyria; it is unlike the other porphyrias. Most cases are due to an acquired enzyme deficiency that is triggered by liver dysfunction.
Protoporphyria (also called erythropoietic protoporphyria), typically begins in childhood or adolescence; sun-exposed skin turns red accompanied by burning and itching, but scarring is uncommon.
Congenital erythropoietic porphyria (CEP), a very rare autosomal recessive disorder; over time, extreme photosensitivity leads to extensive and severe scarring of light-exposed areas.

In rare cases, a patient may have two different porphyrias or a homozygous deficiency of one enzyme that produces a more severe form of porphyria.

Individual Tests
Clinical laboratories measure porphyrins and their precursors in urine, blood, and feces. These tests are listed below:

Delta-aminolevulinic acid (ALA) in urine
Porphobilinogen (PBG) in urine
Porphyrins including uroporphyrins, coproporphyrins, and protoporphyrins in urine, feces, or blood
Zinc protoporphyrin (or free erythrocyte protoporphyrin), one test for protoporphyrins in red blood cells

Specialized laboratories may offer testing for one or more of the affected enzymes. The most commonly measured enzyme is porphobilinogen deaminase (PBG-D) in red blood cells, which tests for patients with acute intermittent porphyria. A few research laboratories offer genetic testing for specific gene mutations that cause one of the porphyrias, but this remains primarily a research tool.

How is the sample collected for testing?

The sample collected depends on the porphyrin tests being ordered. It may be one or more of the following:

A blood sample obtained by inserting a needle into a vein in the arm
A random or 24-hour urine collection (urine must be protected from light during collection)
A fresh stool sample that is not contaminated with urine or water

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

The Test

How is it used?

Porphyrin testing is used to help diagnose and sometimes to monitor porphyrias. Since the symptoms associated with these disorders may also be seen in a variety of other conditions, testing is also used to help rule out the presence of a porphyria in someone who presents with neurologic/psychiatric or cutaneous symptoms.

For acute attacks, porphobilinogen (PBG) and urine porphyrins may be ordered on a random urine sample. If these are abnormal, they are followed by delta-Aminolevulinic Acid (ALA), PBG, and/or porphyrin testing on a 24-hour urine sample. Fecal porphyrins may be ordered to help distinguish between VP and HCP.

For cutaneous porphyrias, whole blood and urine porphyrins are the most frequently ordered tests. They are used to help diagnose a porphyria and may be used to monitor a porphyria. Enzyme testing, such as PBG deaminase, may be ordered to help detect latent porphyrias in family members of a patient with a diagnosed porphyria.

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When is it ordered?

Tests for PBG and porphyrins may be ordered on a random urine specimen when a patient has symptoms that suggest an acute porphyria, such as abdominal pain, nausea, constipation, peripheral neuropathy (tingling, numbness, or pain in the hands and feet), muscle weakness, urinary retention, confusion, and hallucinations. When the initial tests are abnormal, these tests should be repeated on a 24-hour urine collection to determine how much PBG, ALA, and porphyrins are being excreted. Fecal porphyrin testing may be ordered to help distinguish between porphyrias.

Depending upon the patient’s age and symptoms, a test for urine porphyrins and/or the free erythrocyte protoporphyrin test should be ordered when a patient presents with blisters, scarring, redness, or other skin lesions in sun-exposed areas. A positive urine test is followed by analysis of a 24-hour urine collection to determine which porphyrins are present.

Enzyme testing is most commonly ordered to confirm the diagnosis of acute intermittent porphyria (porphobilinogen deaminase in red blood cells). This test is especially helpful in identifying family members of a known patient who have inherited the disease but have not yet developed signs or symptoms. Some reference laboratories can measure porphyrins in plasma, bile or other fluids, but this is not usually necessary to make a diagnosis.

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What does the test result mean?

Care must be taken when interpreting porphyrin test results. Some porphyrins or their precursors may be mildly to moderately elevated in patients with other diseases or conditions. In addition, levels of ALA, PBG and porphyrins may fall to near normal levels between acute attacks of a neurologic porphyria. While negative test results mean that it is unlikely that a patient’s symptoms are caused by a porphyria, positive initial tests should be confirmed with follow-up testing.

ALA and PBG are significantly increased in most patients with an acute porphyria. ALA is less specific than PBG, as it may be elevated in other conditions as well. Specific porphyrins are elevated in each of the porphyrias, and the pattern of elevation (which porphyrin is elevated in which sample) determines the diagnosis. Urine, blood, and stool porphyrins may be increased up to several-fold in a variety of other conditions. Interpretation of the patterns can be difficult. It should be done by a physician or laboratory scientist with expertise in the area.

An abnormal enzyme test or the detection of a gene mutation indicates that a family member has inherited a porphyria. However, enzyme and gene tests cannot determine whether that individual will develop signs and symptoms of porphyria or, if they do, how severe it is likely to be. Fortunately, the majority of gene carriers never have an attack.

Results seen with specific porphyrias include:

Type of Porphyria	Urine ALA and PBG*	Urine porphyrins	Fecal porphyrins	Red Blood Cell Porphyrins
Acute intermittent porphyria	Increased	Increased URO*	Normal	Normal
Variegate porphyria	Increased	Increased COPRO	Increased PROTO, COPRO	Normal
Hereditary coproporphyria	Increased	Increased COPRO	Increased COPRO	Normal
Porphyria curtanea tarda	Normal	Increased URO, 7-carboxyl	Increased Isocoproporphyrin	Normal
Protoporphyria	Normal	Normal	Increased PROTO	Increased PROTO
Congenital erythropoietic porphyria	Normal	Increased URO, COPRO	Increased COPRO	Increased URO, COPRO
URO = Uroporphyrin; COPRO = Coproporphyrin; PROTO = Protoporphyrin
* May be increased only during acute attack

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Is there anything else I should know?

A variety of drugs, alcohol, and other environmental factors such as diets, stress, and illness, can trigger acute attacks of a neurologic porphyria in those with latent or inactive disease. By the same token, sun exposure will induce skin lesions in patients with a cutaneous porphyria. Lifestyle modification to avoid aggravating factors is the most effective way to minimize the impact of a porphyria.

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Common Questions

1. Will latent porphyria affect my health?

In most cases, the answer is no, and the porphyria remains dormant. It is important, however, to have your latent porphyria identified if you have a family history so that your doctor can tailor any medical treatments to avoid drugs and situations that might trigger your porphyria.

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2. Can porphyrin tests be done at home?

No. They require specialized equipment to perform and care in interpretation. Some may be performed in a local hospital laboratory while others may need to be sent to a reference laboratory.

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3. Why does the doctor need a 24-hour urine sample if a random sample has already been tested?

The rate of production and excretion of the porphyrins may vary and may or may not be elevated in a . A allows the evaluation of all of the porphyrin that is excreted in a 24-hour period.

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Related Pages

On This Site

Apart from the Related Tests noted above, there are no other related pages on this site.

Elsewhere On The Web

American Porphyria Foundation (APF)

» See all Article Sources

Article Sources

« Return to Related Pages

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Current Review

Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry, AACC Press, Washington, DC. Pp 439, 440t.

Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp 874-879.

Levin, M. (2007 March 8, Updated). Porphyrins urine. MedlinePlus Medical Encyclopedia. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003614.htm. Accessed on 4/21/08.

Alexander, D. (2007 May 29, Updated). Porphyrins - Blood. MedlinePlus Medical Encyclopedia. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003372.htm. Accessed on 4/21/08.

Frye, R. and DeLoughery, T. (2007 June 26). Pophyria, Acute. emedicine. Available online at http://www.emedicine.com/ped/TOPIC1870.HTM. Accessed on 4/21/08.

(© 2007). About Porphyria and Why laboratory tests are important for diagnosis of porphyrias. American Porphyria Foundation. Available online at http://www.porphyriafoundation.com/about_por/index.html through http://www.porphyriafoundation.com. Accessed on 4/20/08.

Sources Used in Previous Reviews

Schreiber WE. Iron, porphyrin and bilirubin metabolism. In: Clinical Chemistry: Theory, Analysis and Correlation, 4th Ed (LA Kaplan, AJ Pesce, SC Kazmierczak, Eds), CV Mosby, St. Louis, 2003, pp. 657-674.

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosbys Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO. Pp325, 670-672.

(2003 March) Porphyria. NIH Publication No. 03-4632, National Digestive Diseases Information Clearinghouse (NDDIC). Available online at http://digestive.niddk.nih.gov/ddiseases/pubs/porphyria/index.htm through http://digestive.niddk.nih.gov.

(© 2004). Three articles [see below]. American Porphyria Foundation, For Physicians. Available online through http://www.porphyriafoundation.com:
AIP, HCP, VP, & ADP, Diagnosis.
http://www.porphyriafoundation.com/for_physicians/aip/aip02.html
EPP.
http://www.porphyriafoundation.com/for_physicians/epp/epp02.html
PCT.
http://www.porphyriafoundation.com/for_physicians/pct/pct04.html

Cohen, E. (2003 June 5, Update). Porphyria. MedlinePlus Medical Encyclopedia. Available online: http://www.nlm.nih.gov/medlineplus/ency/article/001208.htm.

(© 1995-2004) Porphyrias, Introduction. The Merck Manual 2nd Home Edition, Section 12. Disorders of Nutrition and Metabolism, Chapter 160. Available online at http://www.merck.com/mrkshared/mmanual_home2/sec12/ch160/ch160a.jsp through http://www.merck.com.

(© 1995-2004). Chapter 14. The Porphyrias. The Merck Manual of Diagnosis and Therapy, Section 2. Endocrine And Metabolic Disorders. Available online at http://www.merck.com/mrkshared/mmanual/section2/chapter14/14a.jsp through http://www.merck.com.

(© 2004). Six articles [see below]. ARUP's Guide to Clinical Laboratory Testing. Available online through http://www.aruplab.com
Aminolevulinic Acid (ALA), Urine.
http://www.aruplab.com/guides/clt/tests/clt_al48.jsp#1141880
Porphobilinogen (PBG) Deaminase, Erythrocyte.
http://www.aruplab.com/guides/clt/tests/clt_146b.jsp#1144972
Porphobilinogen (PBG), Urine.
http://www.aruplab.com/guides/clt/tests/clt_147b.jsp#1144990
Porphyrins, Urine.
http://www.aruplab.com/guides/clt/tests/clt_150b.jsp#1145094
Porphyrins, Fecal.
http://www.aruplab.com/guides/clt/tests/clt_149b.jsp#1145074
Porphyrins, Blood and Serum.
http://www.aruplab.com/guides/clt/tests/clt_148b.jsp#1145040