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