Porphyrins

At a Glance

Why Get Tested?

To help diagnose and sometimes to monitor porphyrias (a group of mainly inherited disorders involving disturbance in the formation of haem, a component of haemoglobin)

When To Get Tested?

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

Sample Required?

A blood sample taken from a vein in your arm, a random urine sample and a small stool sample, preferably collected whilst symptoms are occurring

Test Preparation Needed?

None required, but preferably collect the samples whilst symptoms are occurring

On average it takes 7 working days for the blood test results to come back from the hospital, depending on the exact tests requested. Some specialist test results may take longer, if samples have to be sent to a reference (specialist) laboratory. The X-ray & scan results may take longer. If you are registered to use the online services of your local practice, you may be able to access your results online. Your GP practice will be able to provide specific details.

If the doctor wants to see you about the result(s), you will be offered an appointment. If you are concerned about your test results, you will need to arrange an appointment with your doctor so that all relevant information including age, ethnicity, health history, signs and symptoms, laboratory and other procedures (radiology, endoscopy, etc.), can be considered.

Lab Tests Online-UK is an educational website designed to provide patients and carers with information on laboratory tests used in medical care. We are not a laboratory and are unable to comment on an individual's health and treatment.

Reference ranges are dependent on many factors, including patient age, sex, sample population, and test method, and numeric test results can have different meanings in different laboratories.

For these reasons, you will not find reference ranges for the majority of tests described on this web site. The lab report containing your test results should include the relevant reference range for your test(s). Please consult your doctor or the laboratory that performed the test(s) to obtain the reference range if you do not have the lab report.

For more information on reference ranges, please read Reference Ranges and What They Mean.

What is being tested?

Porphyrin tests are assays that are used to help diagnose and monitor a group of rare disorders called porphyrias. Most porphyrin tests detect and measure by-products of the haem synthesis pathway; haem forms part of haemoglobin (the protein inside red blood cells that allows transport of oxygen). The synthesis of haem 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 build up in the body’s fluids and tissues. These precursors are removed from the body in urine and faeces. The precursors that build up are dependent on where the bottleneck is occurring in the pathway i.e. on which enzyme is deficient.

There are eight porphyrias, and each one is associated with a different enzyme deficiency. Most porphyrias are inherited (autosomal dominant) and result from a faulty gene. This results in about a 50% reduction in the activity of the haem-related enzyme. Enough haem is synthesised to prevent the affected person from becoming anaemic, but a large excess of one or more precursors is produced.

Porphyrias may be classified according to

1. The affected enzyme
2. The part of the body where the excess porphyrins are produced:

Hepatic - associated with the liver
Erythropoietic - associated with red blood cell production

3. Signs and symptoms of the disease (either an acute porphyria (severe abdominal pain), cutaneous porphyria (skin sensitivity to sunlight) or some porphyrias have both symptoms and signs.

The acute porphyrias cause acute attacks that are associated with severe abdominal pain, vomiting, nausea, constipation, depression, confusion, hallucinations, and fits. An acute attack usually lasts for no longer than one or two weeks. 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 (skin) porphyrias give sensitivity to sunlight on exposed areas of the skin (photosensitivity). Sunlight exposure, even through a glass window, has a toxic effect on the patient’s skin. This may cause redness, swelling, and a burning sensation in some patients, while in others it leads to blistering, skin thickening, hyperpigmentation (darkening of the skin), and in some cases scarring.

Acute porphyrias include:

Acute intermittent porphyria (AIP), the most common of the acute porphyrias
ALA-dehydratase deficiency porphyria (ADP – also called plumboporphyria), which is an extremely rare condition and in the few cases described is similar to AIP

Acute porphyrias with skin symptoms include:

Variegate porphyria (VP), which is quite rare in the UK, but is particularly common in South African individuals of Dutch descent
Hereditary coproporphyria (HCP) Cutaneous (skin) porphyrias include:
Porphyria cutanea tarda (PCT), the most common of the skin porphyrias; unlike the other porphyrias it may not be inherited and most cases are due to an acquired enzyme deficiency which is triggered by liver dysfunction
Erythropoietic protoporphyria (EPP), which typically begins in childhood or adolescence; sun-exposed skin turns red accompanied by burning and itching, but scarring is uncommon.
X-linked erythropoietic protoporphyria (XLEPP), is clinically similar to EPP
Congenital erythropoietic porphyria (CEP), which is the rarest of the porphyrias (autosomal recessive disorder); over time, extreme photosensitivity leads to extensive and severe scarring of light-exposed areas

Individual Tests

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

Porphobilinogen (PBG) in urine and delta-aminolaevulinic acid (ALA) in urine
Porphyrins and precursors in urine, faeces, or blood

Specialised centres can offer genetic mutation analysis on patients with an unequivocal diagnosis of porphyria or patients who have a family member with a previous, confirmed diagnosis of porphyria.

How is the sample collected for testing?

The sample collected depends on the porphyrin tests being requested. 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 urine sample
A fresh stool sample that is not contaminated with urine or water Samples must be protected from light after collection.

Common Questions

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 acute (severe abdominal pain) or skin symptoms.

For acute attacks, porphobilinogen (PBG) and, sometimes delta-aminolaevulinic acid (ALA), may be requested on a random urine sample. The urine should be collected whilst symptoms are occurring as levels may only be abnormal at this time. All samples must be protected from light. Where positive, faecal porphyrins may be requested to help distinguish between VP and HCP.

For cutaneous (skin) porphyrias, whole blood, plasma and urine porphyrins are the most frequently requested tests. They are used to help diagnose a porphyria, and may be used to monitor treatment.
When is it requested?

PBG (and ALA) may be requested on a random urine sample when a patient has symptoms that suggest an acute porphyria, such as abdominal pain, vomiting, nausea, constipation, peripheral neuropathy (tingling, numbness, or pain in the hands and feet), muscle weakness, urinary retention (not passing urine normally), confusion, and hallucinations. Where positive, faecal porphyrin testing may be requested to help distinguish between porphyrias.

Depending upon the patient’s age and symptoms, a test for urine and blood porphyrins should be requested when a patient presents with blisters, scarring, redness, or other skin lesions in sun-exposed areas.

Genetic testing may be requested to confirm the diagnosis of porphyria and to identify family members of a known patient who may have inherited the disease but have not yet developed signs or symptoms.

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 an acute 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.

PBG is 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, and this should be done by a physician or laboratory scientist with expertise in the area.

The detection of a gene mutation indicates that a family member has inherited a porphyria. However, 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	Faecal 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
Erythropoietic protoporphyria	Normal	Normal	Increased PROTO	Increased PROTO (zinc protoporhyrin)
Congenital erythropoietic porphyria	Normal	Increased URO, COPRO	Increased COPRO	Increased COPRO
X-linked erythropoietic protoporphyria	Normal	Normal	Increased PROTO	Increased zinc and protoporhyrin
ALA-dehydratase deficiency porphyria	Increase in ALA	Normal	Normal	Normal
URO = Uroporphyrins; COPRO = Coproporphyrins; PROTO = Protoporphyrins
* May be increased only during acute attack

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. Click here for a safe list of drugs for those with Acute Porphyria.

Women are more susceptible due to a triggering effect of female hormones, particularly progesterone and attacks may be linked to the menstrual cycle. Oral contraceptive and HRT preparations containing progesterone or related compounds (progestogens) should be avoided, if at all possible, by women with an acute porphyria.

By the same token, sun exposure will induce skin lesions in patients with a skin porphyria. Lifestyle modification to avoid aggravating factors is the most effective way to minimise the impact of a porphyria.
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.