This was adapted from a report I wrote as a final exam for my genetics class.
Porphyria Cutanea Tarda occurs when uroporphyrinogen decarboxylase, an enzyme in the liver needed to synthesize heme, becomes inactivated. This enyzme, which is used in the fourth step of the seven-step heme synthesis pathway, converts uroporphyrinogen III into coproporphyrinogen III by decarboxylating the acetic acid groups in the cytoplasm and converting them into methyl groups, which are transported back to the mitochondria. Inactivation of this enzyme can be triggered by iron, alcohol, estrogens, and infection with hepatitis C or HIV. Also, a partial deficiency of the enzyme can be inheritied, increasing suspectibility to the disorder. This is known as familial PCT. Since iron inhibits the enzyme responsible for PCT, many people will not exhibit symptoms unless they have some sort of systemic iron overload, such as hemochromatosis. Alchohol is another inhibitor of the enzyme.
Affected people get blisters on areas of the skin which are exposed to the sun. It also makes the skin sensitive to minor trauma. Crusting and scarring can also occur and will take a long time to heal. This skin damage happens because of the metabolite porphyrin. Porphyrins are one of the precursors of heme. Since there is a deficiency of this enzyme which is a part of the process which transforms porphyrins and the other heme precursors into heme, the porphyrins aren't getting used up. They accumulate in the liver and are transported to the skin by the blood plasma. When porphyrins are exposed to light and oxygen, they produced a charged, unstable oxygen which is harmful to the skin. PCT can also cause liver damage, including liver cancer and cirrhosis of the liver.
PCT can be diagnosed by testing the blood plasma, urine, and stool for porphyrins. While most porphyrias will cause high levels of porphyrins in the plasma, increased concentrations in urine and stool are characteristic of PCT. However, urine tests will fail if the specimen is not protected from light and kept at a high pH. The urine is likely to be reddish or brownish and will glow pink under a flourescent light; "porphyria" means "purple".
PCT is the most easily treated porphyria. The primary treatment is phlebotomy, where a pint of blood is removed every 1-2 weeks. Phlebotomy reduces the amount of iron in the patient's system, and since iron inhibits the deficient enzyme this is very helpful. Porphyrin levels in the liver and plasma fall and the skin will become normal. It is usually only necessary to perform this treatment five or six times. One can also take very low doses - even lower than normal clinical dosages - of chloroquine or hydroxychloroquine, which remove excess porphyrins from the liver. The patient should also avoid alchohol.
The Genetics of Familial (Type II) PCT
PCT occurs worldwide. It is especially prevalent in the South African Bantu tribe. The gene for familial PCT is located on locus 1p34. There are very few people who are homozygous for PCT. Those that are have a very severe form of the disorder known as Hepatoerythropoietic porphyria (HEP). PCT is autosomal dominant. The gene for type II PCT has been located on choromsome 4 of the mouse and several mutations of the gene are known.
National Digestive Diseases Information Clearinghouse,
- The Porphyrias, Friedlander, Ed, M.D., Pathologist, http://www.pathguy.com/lectures/porphyri.htm
- OMIM Entry 176100 (Familial PCT), National Center for Biotechnology Information, http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?176100
- Porphyrias, The Merck Manual, Section 12, Chapter 141, http://www.merck.com/pubs/mmanual_home/sec12/141.htm
- Heme and Iron, NetBiochem; James Baggot, Ph.D; Sharon E. Dennis, M.S., http://www-medlib.med.utah.edu/NetBiochem/hi.htm and various linked pages