Porphyria

__**Porphyria **__


 * Root Cause: **

Genetic defects resulting in the deficiency of heme biosynthesis enzymes.


 * Affected Physiology: **

The deficiencies may affect the liver (hepatic porphyria) or bone marrow (erythropoietic porphyria) heme sythesis. The accumulation of heme synthetic intermediates affects the photosensitivity of the skin, growth of hair, and neurological system.


 * Figure: A simplified diagram of the Heme synthetic pathway and the enzymes commonly associated with porphyrias. **


 * Background: **

The biochemical cause of porphyria was first detailed by Felix Hoppe-Seyler in the late 1800's. There is a lot of speculation on historical connections to this disease. It is theorized that King George III of England who ruled during the American Revolution may have had the disease. His intermittent erratic behavior and reports of having red colored urine are characteristics of porphyria. It is also argued that some of his descendants have been diagnosed with the hereditary disease. Additionally, there is speculation that porphyria had a hand in the origins of the werewolf and vampire legends, due to similarities between the symptoms and lore. Once again, these are all speculations and have not been proven.


 * Common Symptoms: **

Depending on the type, symptoms include: darkened red, brown or purple excrement on exposure to light, abdominal pain, mental disturbances, extreme light sensitivity - exposure to sunlight can cause rapid onset of rashes and blistering, excessive hair growth in abnormal locations.


 * Standard Treatments: **

Intravenous hematin supplement, high carbohydrate diet to suppress porphyrin production, and recommendation to avoid alcohol, drugs and as much as possible - sunlight.


 * Current Research: **

Since many of the mechanisms that cause porphyria are now understood, current research focuses on reliable diagnoses. The symptoms can be nonspecific and intermittent, often resulting in missed or mistaken diagnosis. A 2011 study, published by Fateen et. al., developed an HPLC and tandem mass spectrometry method for the detection of porphyrin in the urine. This method allowed for the accurate diagnosis of several porphyria subtypes in a group of suspected clinical patients. Other research has recently been conducted to develop reliable means of determining drug safety. It has been discovered that certain drug compounds can induce acute attacks in porphyria patients. Therefore, it is necessary to determine this possibility to provide warnings for afflicted patients to avoid these compounds. Hift et. al. published a review in 2011 on the prediction methods currently employed, which are constantly being refined using collaborative clinical reports.


 * References: **

Voet, D.; Voet, J.G.; Pratt, C.W. Principles of Biochemistry, 3rd ed.; Wiley; Hoboken, NJ, 2008

<span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Fateen, E.; Abd-Elfattah, A.; Gouda, A.; Ragab, L.; Nazim, W. Porphyrins profile by high performance liquid chromatography/electrospray ionization tandem mass spectrometry for the diagnosis of porphyria. Egyptian Journal of Medical Human Genetics 2011, 12 (1), 49-58

<span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Hift, R.J.; Thunell, S.; Brun, A. Drugs in porphyria: From observation to a modern algorithm-based system for the prediction of porphyrogenicity. Pharmacology & Therapeutics 2011, 132 (2), 158-169