To help diagnose and sometimes to monitor porphyrias
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)
The sample type depends on the porphyrin tests ordered by the healthcare practitioner. It may include one or more of the following:
If a neurologic porphyria is suspected, the sample should be collected during an acute attack.
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 levels 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 change (variant). Porphyrias 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.
Experts have not yet reached agreement on whether all porphyrias are inherited. Porphyria cutanea tarda (PCT) may result from genetic or environmental factors such as exposure to certain chemicals or significant liver damage. This type of PCT is termed "acquired" or "sporadic." In patients with acquired PCT, the disorder usually develops after age 30 and onset in childhood is rare.
To diagnose porphyrias, 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 variants that cause one of the porphyrias, but this type of testing is not widely available. If your healthcare practitioner strongly suspects a specific type of porphyria, a sample for genetic testing may be sent to a reference laboratory that performs that type of testing routinely.
- How is the test 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 your signs and symptoms as well as your 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, coproporphyrin, and other intermediate porphyrins 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.
Enzyme testing may be used to confirm a diagnosis of a specific type of porphyria by measuring the activity of the enzymes involved in the heme synthesis pathway. There are eight enzymes in the pathway and each one is related to a specific porphyria type.
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 you have signs and symptoms that your healthcare practitioner suspects are due to a porphyria. Typically, you 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 you have 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
- Peripheral neuropathy—tingling, numbness, or pain in the hands and feet
- Muscle weakness
- Urinary retention
- Confusion, hallucinations
- Red or brown-colored urine
Cutaneous porphyrias—tests may be ordered when you have one or more signs and symptoms affecting sun-exposed areas of the skin, such as:
When you have 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 your 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
Table adapted from: "Iron and porphyrin metabolism," Clinical Chemistry: Theory, Analysis and Correlation, courtesy of William E. Schreiber, MD.
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.
The detection of a gene variant indicates that a family member has inherited a porphyria. However, 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. Similarly, 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.
- Will latent porphyria affect my health?
In most cases, the answer is no, and the porphyria will remain dormant. It is important, however, to have your latent porphyria identified if you have a family history so that your healthcare provider can tailor any medical treatments to avoid drugs and situations that might trigger signs and symptoms.
- Can porphyrin tests be done at my healthcare practitioner's office?
No. Porphyrin tests require specialized equipment and technical skills. Some tests may be performed in a local hospital laboratory, while others may need to be sent to a reference laboratory.
- Why does the healthcare practitioner need a 24-hour urine sample if a random sample has already been tested?
Random samples, which are collected at a single time point, are a useful way of screening for a porphyria. If the screening test is positive, a 24-hour urine sample is collected to give a more accurate measurement of how much porphyrin is excreted during one full day.
- My mother was diagnosed as having porphyria many years ago but has not had any symptoms since then. Why is this?
It may be that her disease has been quiet all this time. It is also possible that the diagnosis made back then was incorrect. Testing for porphyria many years ago was not as accurate and some people may have been diagnosed incorrectly.
- When I look on the Internet for information about safe and unsafe drugs, different sites use different classifications and the lists are not the same. Why is this?
Information on the safety of drugs in porphyria is incomplete. Porphyria is a rare disease and many new drugs have been introduced in recent years. Thus, it is often not possible to be sure that a drug is safe until it has been used safely in many patients with porphyria, and this may take years to establish.