Porphyria

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 erythropoetic porphyrias, based on the site of the overproduction and mainly accumulation of the porphyrins (or their chemical precursors).

Table of contents

1 Overview 2 Subtypes 2.1 Hepatic porphyria 2.2 Erythropoetic porphyia 2.3 Porphyria variegata 3 Signs and symptoms 4 Diagnosis 5 Porphyria and vampirism 6 External link

Overview

\nIn 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

\nThere 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\n# δ-aminolevulinate (ALA) dehydratase\n# hydroxymethylbilane (HMB) synthase\n# uroporphyrinogen (URO) synthase\n# uroporphyrinogen (URO) decarboxylase\n# coproporphyrinogen (COPRO) oxidase\n# protoporphyrinogen (PROTO) oxidase\n# ferrochelastase

Hepatic porphyria

\nThe hepatic porphyrias include:\n* ALA dehydratase deficiency\n* acute intermittent porphyria (AIP): a deficiency in HMB synthase\n* hereditary coproporphyria (HCP): a deficiency in COPRO oxidase\n* variegate porphyria (VP): a deficiency in PROTO oxidase\n* porphyria cutanea tarda (PCT): a deficiency in URO decarboxylase

Erythropoetic porphyia

\nThe erythropoetic porphyrias include:\n* X-linked sideroblastic anemia (XLSA): a deficiency in ALA synthase\n* congenital erythropoietic porphyria (CEP): a deficiency in URO synthase\n* erythropoietic protoporphyria (EPP): a deficiency in ferrochelatase

Porphyria variegata

\nVariegate 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 actue 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

\nThe hepatic porphyrias primarily affect the nervous system, resulting in abdominal pain, neuropathy, seizures, and mental disturbances, including hallucinations, depression, anxiety, and paranoia. 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 reddish or purple hue. Attacks of the disease can be triggered by drugs (barbiturates, tranquilizers, oral contraceptives, sedatives), chemicals, certain foods, and exposure to the sun.

Diagnosis

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

Porphyria and vampirism

\nPorphyria has been speculatively linked with the vampirism myth, based on a number of superficial resemblances between the symptoms of the porphyrias and vampire folklore. These fancies are based on a misunderstanding of the nature of porphyria. Porphyria is also inadequate as an explanation for werewolf beliefs.

External link

\n* Debunking the association of porphyria with vampirism