INDEPENDENT RESEARCH AT TRINITY WASHINGTON UNIVERSITY

What is PXE?

Pseudoxanthoma elasticum (PXE)  is a genetic disorder that is characterized by the deposit of calcium and phosphate (mineralization) into the elastic fibers  which is composed of connective tissues in numerous organs such as skin, eyes, arterials vessels and other areas like the digestive tract.

 

Symptoms that lead to diagnosis

The skin lesions consist of small yellowish bumps in rows or a lacy pattern, which may join to make large patches and most commonly appear on the side of the neck and progress through different parts of the body. The eye lesions, the angioid streaks affect the retina for most patients with PXE between the ages 20 to 40. The Angioid streaks may lead to progressive visual failure which would eventually led to a central vision loss. The common manifestations of arterial disease in PXE may lead to pain in the legs on walking (claudication), stroke, heart pain (angina) and cardiomyopathy (heart muscle disease).

 

 

 

 

 

 

 

 

 

http://disorders.eyes.arizona.edu/disorders/pseudoxanthoma-elasticum         http://www.aocd.org/?PseudoxanthomaElast

 

 

 

 

 

 

 

          

 

 

                                                                                           http://www.pxe.org/what-pxe

 

 

 

How common is the disease?

 

The approximate range of infected people with PXE goes from 1 in 100,000 people to 1 in 25,000. However, there is no exact estimate of individuals with PXE in a population because it is very likely that many individuals have not be diagnosed, particularly people with mild signs of PXE or those whose signs are not distinctive.

 

What causes PXE?

 

PXE is cause by mutations that occurs in a gene called ABCC6. It provides instructions for making a protein called multidrug resistance-associated protein 6 (MRP6, also known as the ABCC6 protein), found primarily in kidney and liver cells. MRP6 is a putative membrane transport protein and its function have not been defined yet. The ABCC6 gene is part of the ATP Binding Cassette (ABC) protein family. ABCC6 mutation was detected through the use of the positional cloning DNA (cDNA) that provide solid evidence for the linkage of the short arm of chromosome 16p13.1 which is where the ABCC6 genes is found.

 

Mutations in the ABCC6 gene lead to an absent or nonfunctional MRP6 protein, which may impair the transport of particular substances into the blood for distribution to other parts of the body. It is unclear how ABCC6 gene mutations lead to the mineralization of elastic fibers and the characteristic features of Pseudoxanthoma elasticum.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

                                         http://www.pxe.org/summary-2010-pxe-international-research-meeting

 

 

 

Inheritance of the ABCC6     gene

 

PXE disease is a heritable autosomal recessive disease. PXE is autosomal recessive because the progression of the disease has minimal manifestations and it was suggested that the presence of autosomal recessive traits are necessary in families that are heterozygous carriers. A disease is to be heritable when it is passed on from parents to children and sometimes there is an apparent of physical and genetic changes on looks and the growths of the skin, bones, joints, heart, blood vessels, lungs, eyes, and ears.

 

Can PXE be treated?

 

There is no cure for PXE, there are some treatments recommended at hand to minimize the rate of the genetic disease.

• blood vessels: Regular follow-up with a specialist vascular surgeon and/or cardiologist is recommended.

• Skin lesions: plastic surgery to improve the appearance of the skin.

• Restriction of dietary calcium has been tried with some benefit, but this is controversial

• Laser photocoagulation may be helpful in preventing further bleeding at the back of the eye.

• The genetic counselling may be helpful if the individual with PXE is worry of passing this gene to the next generation.

• DNA Banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Individuals with PXE disease are encouraged to give thier for further research about this genetic disease.

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There are multiple  mechanisms that activate the development of the ABCC6 gene mutations in PXE disease.  This disease is due to an absence of a certain circulating factors in the blood in which scientists have not identified the factor. The PXE disease does not have a cure but there are treatments that can be given to reduce the rate of the disease.