Porphyria

Overview

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

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:
9. ALA dehydratase deficiency
10. acute intermittent porphyria (AIP): a deficiency in HMB synthase
11. hereditary coproporphyria (HCP): a deficiency in COPRO oxidase
12. variegate porphyria (VP): a deficiency in PROTO oxidase
13. porphyria cutanea tarda (PCT): a deficiency in URO decarboxylase
    

    Erythropoetic porphyria

    
    The erythropoetic porphyrias include:
14. X-linked sideroblastic anemia (XLSA): a deficiency in ALA synthase
15. congenital erythropoietic porphyria (CEP): a deficiency in URO synthase
16. 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.

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 sufferers as vampires and werewolves

History

Reference