Inherited disorders: Porphyria
These pages about porphyria were updated in partnership with the UK Porphyria Medicines Information Service, Cardiff and the Cardiff Porphyria Service. We'd like to thank these partners for contributing their clinical expertise and support.
Porphyrias are a group of inherited metabolic disorders of the haem biosynthesis pathway. Haem synthesis involves multiple enzymatic steps which convert haem precursors into haem. Haem is a molecule created by human metabolism and is used to build larger molecules such as haemoglobin, myoglobin, and cytochrome. Porphyrias occur when there is a deficiency (or in the case of one porphyria an increase in activity) of one of the enzymes involved in haem synthesis. This disruption leads to accumulation of of neurotoxic and/or phototoxic haem precursors, and so these conditions are characterised by acute neurological and visceral symptoms ('neurovisceral crises') and/or skin lesions.
What type of porphyria?
It is important to understand the type of porphyria your patient has been diagnosed with, and in particular whether it is acute porphyria or non-acute porphyria. Non-acute porphyrias are also known as cutaneous porphyrias.In practice, acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HCP) are the conditions that pharmacists may see presenting acutely. Many factors can precipitate an acute attack by increasing the body's need for haem, and they act cumulatively as shown in the diagram below. In patients with porphyria the haem is produced, but precursors in the pathway may accumulate and cause symptoms. In addition, several patient factors can predispose individuals to developing an attack.
Four types of acute porphyrias affect the nervous system (AIP, VP, HCP, ADP). Two of these can also affect the skin (VP,HCP). Symptoms for acute porphyrias develop over hours or days and last for days or weeks.
Early symptoms of an acute attack can include acute severe abdominal pain, nausea and vomiting, constipation, autonomic instability and peripheral motor neuropathy. This may progress to severe neurological and psychiatric symptoms, and a progressive, irreversible neuropathy. Ultimately, this can be fatal if untreated.
Non-acute (cutaneous) porphyria affect only the skin. The most common is PCT and this can cause chronic symptoms which include fragility and blistering. Patients with EPP develop acute pain after their skin is exposed to sunlight. CEP is a severe blistering porphyria with multi-system involvement.