The porphyrias are inherited or acquired disorders of certain enzymes in the heme biosynthetic pathway (also called porphyrin pathway). They are broadly classified as hepatic porphyrias or erythropoietic porphyrias, based on the site of the overproduction and mainly accumulation of the porphyrins (or their chemical precursors).

Overview

In humans, porphyrins are the main precursors of heme, an essential constituent of hemoglobin, myoglobin and cytochrome.

Deficiency in the enzymes of the porphyrin pathway leads to insufficient production of heme. This is, however, not the main problem; most enzymes - even when less functional - have enough residual activity to assist in heme biosynthesis. The largest problem in these deficiencies is the accumulation of porphyrins, the heme precursors, which are toxic to tissue in high concentrations. The chemical properties of these intermediates determine in which tissue they accumulate, whether they are photosensitive, and how the compound is excreted (in the urine or feces).

Subtypes

There are eight enzymes in the heme biosynthetic pathway: the first and the last three are in the mitochondria, while the other four are in the cytosol.

1. δ-aminolevulinate (ALA) synthase
2. δ-aminolevulinate (ALA) dehydratase
3. hydroxymethylbilane (HMB) synthase
4. uroporphyrinogen (URO) synthase
5. uroporphyrinogen (URO) decarboxylase
6. coproporphyrinogen (COPRO) oxidase
7. protoporphyrinogen (PROTO) oxidase
8. ferrochelastase

Hepatic porphyria

The hepatic porphyrias include:

• ALA dehydratase deficiency
• acute intermittent porphyria (AIP): a deficiency in HMB synthase
• hereditary coproporphyria (HCP): a deficiency in COPRO oxidase
• variegate porphyria (VP): a deficiency in PROTO oxidase
• porphyria cutanea tarda (PCT): a deficiency in URO decarboxylase

Erythropoetic porphyria

The erythropoetic porphyrias include:

• X-linked sideroblastic anemia (XLSA): a deficiency in ALA synthase
• congenital erythropoietic porphyria (CEP): a deficiency in URO synthase
• erythropoietic protoporphyria (EPP): a deficiency in ferrochelatase

Porphyria variegata

Variegate porphyria (also porphyria variegata or mixed porphyria) results from a partial deficiency in PROTO oxidase , manifests itself with skin lesions similar to those of porphyria cutanea tarda combined with acute neurologic attacks. It may first occur in the second decade of life; there is a cohort of sufferers living in South Africa descended from a single ancestor from the Netherlands, Berrit Janisz, who emigrated in the 17th century.

Signs and symptoms

The hepatic porphyrias primarily affect the nervous system, resulting in abdominal pain, neuropathy, seizures, and mental disturbances, including hallucinations, depression, anxiety, and paranoia. Cardiac arrhythmias may develop as the autonomic nervous system is affected. Constipation is frequently present, as the nervous supply to the gut is affected.

The erythropoeitic porphyrias primarily affect the skin, causing photosensitivity, blisters, itching, and swelling.

In some forms of porphyria, accumulated heme precursors excreted in the urine may change its color to a fluorescent reddish or purple hue.

Attacks of the disease can be triggered by drugs, e.g. barbiturates, tranquilizers, oral contraceptives, sedatives, certain antibiotics, chemicals, certain foods, and exposure to the sun.

Diagnosis

Porphyria is diagnosed through tests on blood, urine, and stool. It can be treated with medicines to relieve symptoms, a drug called hematin (which is like heme), or a high-carbohydrate diet .

Porphyria sufferers as vampires and werewolves

Porphyria has been suggested as an explanation for the origin of vampires and werewolves, based upon a number of superficial similarities between the condition and the legends. These ideas developed from a misunderstanding of the nature of porphyria and concentrate more on the traits of modern vampire and werewolf fiction than on the original folklore beliefs.

History

Modern medicine has suggested that the insanity exhibited by King George III was the result of porphyria. Recent research has shown that porphyria is another hereditary disease plaguing the British royal family (besides hemophilia). Research has shown that both James I and Mary I of Scotland probably suffered from the disease. Queen Anne of Great Britain suffered from the disease as well. Queen Victoria's granddaughter Charlotte (a sister of Wilhelm II) and Prince William of Gloucester also suffered from the disease.

Reference

• Kauppinen R. Porphyrias. Lancet 2005;365:241-52. PMID 15652607.

External link

• Debunking the association of porphyria with vampirism (from The Straight Dope)