This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at University of Wisconsin-Madison
F-PCT is a type of porphyria, or a set of disorders that result in abnormal synthesis of heme, that is also known as type 2 PCT or vampires’ disease. It is a disease characterized by blisters on sun-exposed skin (photosensitivity), liver abnormalities, skin fragility after minor trauma, excessive facial hair (hypertrichosis), and hyperpigmentation. The cause of F-PCT symptoms is due to the bodies inability to produce functional uroporphyrinogen decarboxylase (UROD), which normally function in the heme biosynthesis pathway. [1]
Function of UROD in F-PCT and the Heme Biosynthesis Pathway
Heme is an iron-containing molecule that is found in both plants and animals. Specifically, heme is found in hemoproteins such as hemoglobin and myoglobin or more commonly known as red blood cells and muscle cells, respectively [2]. The iron molecule found inside heme, functions to bind and carry oxygen, among other things. The development of F-PCT occurs typically in mid-to-late stages of life, due to a mutation in the UROD gene resulting in the production of deficient or inefficient UROD proteins. The UROD gene plays a role in the heme biosynthesis pathway, specifically the conversion of uroporphyrinogen III into coproporphyrinogen III. When F-PCT manifests, porphyrins accumulates in the body. Porphyrins, that accumulate in skin, when exposed to sun may become excited and cause local damage. [3]
|
Heme Visualization
|
Uroporphyrinogen III Coproporphyrinogen III
Risk Factors
F-PCT is autosomal dominantly inherited, but due to low penetrance is expressed 50% in offspring of a single pathogenic UROD parent. More importantly, the development of F-PCT is multifactorial, which means that the heterozygous Inheritance the UROD mutation may not be sufficient to cause the development of F-PCT. Other risk factors contribute to the efficiency of UROD proteins and thus the manifestation of F-PCT. Factors such as alcohol use, iron overload, smoking, HIV, and/or Hepatitis C are associated with F-PCT expression. [1] These factors cause increased reactive oxidative species (ROS) that can promote UROD inhibitor - porphomethene from accumulated porphyrins [insert cite]. Accumulation of porphomethene causes further decrease in UROD activity exacerbating symptoms of F-PCT. |
Gap in Knowledge
It is understood that when UROD levels drop to 20% below normal, F-PCT may develop. [3] However, It is not currently understood how these multiple risk factors cause F-PCT to develop. Furthermore the role of stress in regulation UROD in normal heme biosynthesis is unknown.
Other gaps in knowledge:
- Is it possible to introduce UROD proteins as a method for clinical treatment?
- What are the underlying genetic factors contribute to susceptibility?
Further Information
For further information on F-PCT, its risks, treatment options, and consultation please visit the American Porphyria Foundation (APF).
References:
1. Liu, L. U. (2013, June 6). Heme biosynthesis. Retrieved February 24, 2021, from https://www.frontiersci.com/heme-biosynthesis
2. Ogun, A. S. (2020, July 10). Biochemistry, heme synthesis. Retrieved February 24, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK537329/
3. G;, K. (n.d.). Porphyrias and PHOTOSENSITIVITY: Pathophysiology for the clinician. Retrieved February 25, 2021, from https://pubmed.ncbi.nlm.nih.gov/30296862/
Images shown in the symptoms page are all produced using BioRender.
2. Ogun, A. S. (2020, July 10). Biochemistry, heme synthesis. Retrieved February 24, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK537329/
3. G;, K. (n.d.). Porphyrias and PHOTOSENSITIVITY: Pathophysiology for the clinician. Retrieved February 25, 2021, from https://pubmed.ncbi.nlm.nih.gov/30296862/
Images shown in the symptoms page are all produced using BioRender.
Contact Information |
Genetic Building 25g Henry Mall Madison, WI 53703 |