Back Blood-tests Explained

Porphyrins

At a Glance

Why Get Tested?

To help diagnose and sometimes to monitor porphyrias

When to Get Tested?

When you have symptoms that suggest a neurologic porphyria (e.g., abdominal pain, tingling or numbness in the hands or feet, muscular weakness and/or alterations in thought or mood) or a cutaneous porphyria (e.g., redness, blistering, or scarring of 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?

If a neurologic porphyria is suspected, the sample should be collected during an acute attack.

The Test Sample

What is being tested?

Porphyrins are a group of compounds defined by their chemical structure. These compounds are by-products of heme synthesis and are normally present at low concentrations in blood and other body fluids. Porphyrin tests measure porphyrins and their precursors in urine, blood, and/or stool.

Heme is an iron-containing pigment that is a component of hemoglobin and a number of other proteins. It consists of an organic portion (protoporphyrin) bound to an iron atom. 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, the process is impeded and intermediate porphyrins such as uroporphyrin, coproporphyrin, and protoporphyrin build up in the body's fluids and tissues. The precursors that accumulate depend on which enzyme is deficient, and they can exert toxic effects.

Porphyrin tests are used to help diagnose and monitor a group of disorders called porphyrias. There are seven types of porphyria, and each one is associated with a different enzyme deficiency. Most porphyrias are inherited, the result of a gene mutation. They may be classified according to the signs and symptoms of the disease as neurological, cutaneous, or both.

The porphyrias that cause neurological symptoms present with acute attacks lasting days or weeks. Signs and symptoms during the attack include abdominal pain, constipation, confusion, hallucinations, and/or seizures. There are four neurologic porphyrias: acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and the very rare ALA dehydratase deficiency porphyria (ADP). Some cases of VP and HCP may also have skin-related symptoms.

The cutaneous porphyrias are associated with photosensitivity that causes redness, swelling, a burning sensation, blistering, skin thickening, hyperpigmentation, and/or scarring. There are three cutaneous porphyrias: porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP), and congenital erythropoietic porphyria (CEP). For more information about each disease, see the article on Porphyria.

To diagnose porphyrias, clinical laboratories measure porphyrins and their precursors in urine, blood, and/or stool. Testing may include measurement of one or more of the following:

Porphobilinogen (PBG), a porphyrin precursor, in urine
Delta-aminolevulinic acid (ALA), another porphyrin precursor, in urine
Porphyrins (uroporphyrin, coproporphyrin, and protoporphyrin) in urine, blood, or stool

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 acute intermittent porphyria. A few laboratories offer genetic testing for specific gene mutations that cause one of the porphyrias, but this type of testing is not widely available.

How is the sample collected for testing?

The sample type depends on the porphyrin tests ordered by the healthcare practitioner. It may include 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

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

If a neurologic porphyria is suspected, the sample should be collected during an acute attack.

The Test

How is it used?
When is it ordered?
What does the test result mean?
Is there anything else I should know?

How is it used?

Porphyrin testing is used to help diagnose and sometimes to monitor porphyrias. These disorders can be classified into two groups based on signs and symptoms: neurologic porphyrias and cutaneous porphyrias. As some porphyrias can have similar symptoms, testing is also used to help determine which type is present. A healthcare practitioner will choose individual tests based on the affected person's signs and symptoms as well as the medical and family history.

Neurologic porphyrias are associated with acute attacks involving the nervous system and/or gastrointestinal tract. They include acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HCP), and ALA dehydratase deficiency porphyria (ADP).

Tests for neurologic porphyrias are given below:

A urine test for porphobilinogen (PBG), a porphyrin precursor, is the primary test.
If the result of the PBG test is abnormal, urine porphyrin testing, which measures uroporphyrin and coproporphyrin, may be ordered to provide additional information on the type of neurologic porphyria that is present.
A test to detect porphyrins in stool may be used to help distinguish between VP and HCP.
Aminolevulinic acid (ALA), another porphyrin precursor, is used to diagnose the rare ALA dehydratase deficiency porphyria. ALA may be ordered along with PBG as part of the diagnostic workup, as it is usually elevated in all four of the neurologic porphyrias.

Cutaneous porphyrias produce skin-related symptoms. This type includes porphyria cutanea tarda, (PCT), erythropoietic protoporphyria (EPP) and congenital erythropoietic porphyria (CEP).

Tests for cutaneous porphyrias are given below:

Urine porphyrin testing is ordered to evaluate adults with blisters, scarring and hyperpigmentation in sun-exposed areas of the skin (suspected PCT).
A blood test for porphyrins is the best test to diagnose patients with EPP, who present with redness, itching and swelling that begins soon after sun exposure.
Both blood and urine tests for porphyrins are abnormal in CEP, a rare disorder that produces extreme sensitivity to light in children.

These tests may sometimes be used to monitor the disease in patients who have been diagnosed with a porphyria.

Enzyme testing may be used to confirm the diagnosis of acute intermittent porphyria (by measuring porphobilinogen deaminase in red blood cells). Genetic testing for porphyria is not widely available, but it is another way to establish the diagnosis. Both types of tests may be used to identify family members who have inherited a porphyria, even if they do not have signs and symptoms of the disease.

When is it ordered?

Porphyrin tests are ordered when an individual has signs and symptoms that a healthcare practitioner suspects are due to a porphyria. Typically, the person will have either neurologic symptoms or skin-related symptoms, but those with VP or HCP may have both.

Acute neurologic porphyrias—tests may be ordered when someone has acute attacks lasting for days to weeks. The attacks may be triggered by a variety of drugs or environmental factors such as dietary changes, stress, and exposure to toxic substances. The attacks may include signs and symptoms, such as:

Abdominal pain, nausea
Constipation
Peripheral neuropathy—tingling, numbness, or pain in the hands and feet
Muscle weakness
Urinary retention
Confusion, hallucinations

Cutaneous porphyrias—tests may be ordered when someone has one or more signs and symptoms affecting sun-exposed areas of the skin, such as:

Blisters
Scarring
Hyperpigmentation
Redness
Itching
Burning
Swelling

When an individual has been diagnosed with a porphyria, testing may be performed on a regular basis to monitor the condition.

What does the test result mean?

Care must be taken when interpreting porphyrin test results. Results are typically reported as below an established threshold (normal) or, if increased, reported as a specific level.

One or more of the porphyrins and their precursors are usually elevated in each of the porphyrias, and the pattern of elevation (which porphyrin is elevated in which sample) helps determine the diagnosis. For example, urine PBG is significantly increased in people with a neurologic porphyria. However, porphyrins may be increased up to several-fold in a variety of other conditions. In addition, levels may fall to near normal levels between acute attacks of a neurologic porphyria. Interpretation of the patterns can be difficult and should be done by a physician or laboratory scientist with expertise in porphyrias.

If the initial test results are negative, it means that it is unlikely that a person's symptoms are caused by a porphyria. Initial tests that are positive should be confirmed with follow-up testing.

People usually do not need to have all of these tests performed. The following table summarizes the patterns of results that are typical for each type of porphyria:

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
ALA dehydratase deficiency	Increased ALA only	Increased COPRO		Increased PROTO
Porphyria cutanea tarda	Normal	Increased URO, 7-carboxyl	Increased Isocoproporphyrin	Normal
Erythropoietic Protoporphyria	Normal	Normal	Increased PROTO	Increased PROTO
Congenital erythropoietic porphyria	Normal	Increased URO, COPRO	Increased COPRO	Increased URO, COPRO
PBG = Porphobilinogen; ALA = Aminolevulinic acid; URO = Uroporphyrin; COPRO = Coproporphyrin; PROTO = Protoporphyrin
* May be increased only during acute attack

If enzyme testing is performed, a low level of the enzyme can help confirm a diagnosis. For example, a decreased level of porphobilinogen deaminase confirms the diagnosis of acute intermittent porphyria.

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 the porphyria or, if the person does, how severe they are likely to be. Fortunately, the majority of gene carriers never have an attack.

Is there anything else I should know?

The diagnosis of a porphyria can be difficult. As a group, these diseases are uncommon or rare, and the signs and symptoms can be seen mimic other, more common diseases.

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 can induce skin lesions in people with a cutaneous porphyria. Lifestyle modifications to avoid aggravating factors are the most effective way to minimize the impact of a porphyria.

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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