Porphyrias are a group of rare metabolic diseases in which heme metabolism is altered.


Porphyria is rare, with some forms being extremely rare. Estimates for the prevalence of the disease vary in the literature and could reflect differing geographic distribution and/or incomplete reporting.

Acute intermittent porphyria has a prevalence of 1 in 1600 Caucasians but a low clinical penetrance of approximately 2-3% . Globally it is thought to occur in 5 to 10 per 100,000 .

The most common type of porphyria is porphyria cutanea tarda.


Porphyrin can be overproduced in the liver or bone marrow, therefore some authors classify porphyrias as erythropoietic or hepatic according to the main site of overproduction of heme precursors :

  • acute hepatic porphyrias
    • subtypes:
      • acute intermittent porphyria
      • hereditary coproporphyria
      • variegate porphyria
      • 5-aminolevulinic acid dehydratase deficiency porphyria (also known as plumboporphyria or Doss porphyria)
    • greater frequency in females (~4:1)
    • inheritance is either autosomal recessive and autosomal dominant depending on subtype
    • predominantly neurovisceral symptoms
  • chronic hepatic porphyrias
    • subtypes:
      • hepatoerythropoietic porphyria
      • porphyria cutanea tarda
    • greater frequency in males
    • usually acquired although may be autosomal recessive
    • causes cutaneous lesions
  • erythropoietic porphyrias
    • subtypes:
      • X-linked protoporphyria
      • congenital erythropoietic protoporphyria
    • affects males and females equally
    • inheritance is autosomal dominant or X-linked depending on subtype

Clinical presentation

The clinical presentation is non-specific and variable, depending on the type of porphyria. Generally, the most common symptoms being abdominal pain (74%), back pain (56%), chest pain (58%), and nausea and vomiting (73%) , however, there can be a wide range of neuropsychiatric and cutaneous manifestations as well.

Some porphyrias are considered acute due to acute attacks as the presentation, and of these, acute intermittent porphyria is the most common . Intermittent attacks of neurological or psychiatric symptoms accompanied by abdominal pain could be suspicious for a porphyria such as this, especially if triggered by a drug with hepatic metabolism.


Porphyrin is a part of heme, which is, in turn, a part of hemoglobin as well as some other biologically important molecules. The pathophysiology of acute attacks is complex and varies depending on subtype. It is postulated that raised concentrations of aminolevulinic acid and porphobilinogen cause neurotoxicity either directly, by interacting with receptors structurally similar to gamma-aminobutyric acid, or by forming free radicals and reactive oxygen species .

Radiographic features

Although porphyrias are not usually radiographically visible, posterior reversible encephalopathy syndrome can be associated with acute intermittent porphyria .

Treatment and prognosis

Patients should be counseled on avoidance of triggers and monitored for long term complications including hepatocellular carcinoma . Approximately 20% of patients with recurrent attacks develop chronic pain . Liver transplant may be curative for acute intermittent porphyria in patients with severe recurrent attacks . Newer treatment methods are under development including small interfering ribonucleic acid (RNA) that aim to downregulate aminolevulinic acid synthase-1 .

History and etymology

The term "porphyria" comes from the Greek 'porphyros', which means purple. Many believe Hippocrates of Kos (460-377 BCE) to have described the disease in Case XI from his “Epidemics Book III” regarding a young Greek woman from Thasos. It is now thought that this case represented acute intermittent porphyria . Archibald L Cochrane (1909-1988) , one of the most important figures in modern medicine, suffered from porphyria, and some speculate the disease may have been the impetus for his scientific approach to medicine.