Porphyrins

Porphyrin tests are assays that are used to help diagnose, and monitor a group of disorders called porphyrias. Most porphyrin tests detect and measure by-products of the synthesis of haem, a part of haemoglobin (the protein inside red blood cells that allows them to transport oxygen) and a number of other proteins. 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 and are removed in urine and faeces. Which precursors build up depends on where the bottleneck is.

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 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

or
   3. Signs and symptoms of the disease (abdominal pain, neurological / psychiatric, skin, 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, sickness, constipation, depression, confusion, hallucinations, and fits. 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 are associated with 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 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 (skin) porphyrias include:

• Porphyria cutanea tarda (PCT), the most common porphyria; unlike the other porphyrias, most cases are due to an acquired enzyme deficiency which is triggered by liver dysfunction.
• Protoporphyria (also called erythropoietic protoporphyria), which 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 faeces. These tests are listed below:

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

Specialised 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. 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.

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 collection (urine must be protected from light during collection)

A fresh stool sample that is not contaminated with urine or water