Porphyria

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

Epidemiology

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

Recent research suggests that acuteAcute intermittent porphyria has a prevalence of 1 in 1600 Caucasians but a low clinical penetrance of approximately 2-3% ⁸. Globally it is thought to occur in 5 to 10 per 100 000,000 ⁸.

The most common type of porphyria is porphyria cutanea tarda.

Classification

Porphyrin can be over producedoverproduced in the liver or bone marrow, and therefore some sources classify porphyrias as erythropoietic or hepatic according to the main site of over productionoverproduction of heme precursors ⁸:

• acute hepatic porphyrias
  • sub typessubtypes: acute intermittent porphyria, hereditary croproporphyriacoproporphyria, variegate porphyria, 5-aminolevulinic acid dehydratase deficiency porphyriaalso also known as plumboporphyria (rare)
  • greater frequency in females (~ 4~4:1)
  • liver is main site of heme precursor overproduction
  • inheritance is both autosomal recessive and autosomal dominant depending on sub typesubtype
  • predominantly neurovisceral symptoms
• chronic hepatic porphyrias
  • sub typessubtypes: hepatoerythropoietic porphyria, porphyria cutanea tarda
  • greater frequency in males
  • liver is main site of heme precursor overproduction
  • usually acquired although may be autosomal recessive
  • causes cutaneous lesions
• erythropoietic porphyrias
  • sub typessubtypes: X-linked protoporphyria, congenital erythropoietic protoporphyria
  • effects males and females equally
  • erythroblasts are main site of heme precursor overproduction
  • inheritance is autosomal dominant or X-linked depending on sub typesubtype

Clinical presentation

The clinical presentation is non-specific with the most common symptoms being abdominal pain (74%), back pain (56%), chest pain (58%), and nausea and vomiting (73%) ^8,10.

Clinically distinguishing between porphyrias with neurological manifestations and porphyrias with cutaneous manifestations, is somewhat useful. However, some porphyrias have both cutaneous and neurological manifestations. Some porphyrias are considered acute due to acute attacks as the presentation, and of these, acute intermittent porphyria (AIP) is the most common ¹. Intermittent attacks of neurological or psychiatric symptoms accompanied by abdominal pain could be suspicious for a porphyria, especially if triggered by a drug with hepatic metabolism. Cutaneous porphyrias typically present with photosensitivity and skin lesions.

Pathology

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 sub typesubtype. 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 ⁹.

Radiographic features

Although porphyrias are not alwaysusually radiographically visible, posterior reversible encephalopathy syndrome is associated with acute intermittent porphyria ^2-4.  

Treatment and prognosis

Patients should be counseled on avoidance of triggers and monitored for long term complications including hepatocellular carcinoma (HCC) ^8,9. Approximately 20% of patients with recurrent attacks develop chronic pain ⁸. Liver transplant may be curative for acute intermittent porphyria in patients with severe recurrent attacks ⁹.  Newer treatment methods are under development including small interfering ribonucleic acid (RNA) that aim to down regulatedownregulate aminolevulinic acid synthase-1 ⁸.

History and etymology

The term "porphyria" comes from the Greek 'porphyros', which means purple. Many believe Hippocrates of Kos (460-377 BCE) ⁶ to have described the disease in Case XI from his “Epidemics Book III” about a young Greek woman from Thasos. It is now thought that this case represented acute intermittent porphyria ⁷. Archibald L Cochrane, (1909-1988) ⁵, 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.