Pseudoxanthoma elasticum

Definition

Pseudoxanthoma elascticum (PXE) is an inherited connective tissue disorder in which the elastic fibers present in the skin, eyes, and cardiovascular system gradually become calcified and inelastic.

Description

It is estimated that approximately 2,500-5,000 people in the United States are afflicted with this rare disorder, which is also referred to as Grönblad-Strandberg-Touraine syndrome and systemic elastorrhexis.

The course of PXE varies greatly between individuals. Typically it is first noticed during adolescence as yellow-orange bumps on the side of the neck. Similar bumps may appear at other places where the skin bends a lot, like the backs of the knees and the insides of the elbows. The skin in these areas tends to get thick, leathery, inelastic, and acquire extra folds. These skin problems have no serious consequences, and for some people, the disease progresses no further.

Bruch's membrane, a layer of elastic fibers in front of the retina, becomes calcified in some people with PXE. Calcification causes cracks in Bruch's membrane, which can be seen through an ophthalmoscope as red, brown, or gray streaks called angioid streaks. The cracks can eventually (e.g., in 10-20 years) cause bleeding, and the usual resultant scarring leads to central vision deterioration. However, peripheral vision is unaffected.

Arterial walls and heart valves contain elastic fibers that can become calcified. This leads to a greater susceptibility to the conditions that are associated with hardening of the arteries in the normal aging population--high blood pressure, heart attack, stroke, and arterial obstruction--and, similarly, mitral valve prolapse. However, the overall incidence of these conditions is only slightly higher for people with PXE than it is in the general population.

Arterial inelasticity can lead to bleeding from the gastrointestinal tract and, rarely, acute vomiting of blood.

Causes & symptoms

PXE is caused by genetic material irregularities that are inherited in either a dominant or recessive mode. A person with the recessive form of the disease (which is most common) must possess two copies of the PXE gene and, therefore, must have gotten one from each parent. In the dominant form, one copy of the defective gene is sufficient to cause the disease, so a person with the dominant form must have inherited it from a parent with PXE. PXE inheritance is not sex-linked. This means that males and females can inherit a gene for PXE from either parent.

The genetic aspect of this condition is not well understood. Experts disagree on the number of different forms of PXE; some argue for the existence of two variants, others for five. At least two forms of PXE, one dominant and one recessive, are caused by defects in what appears to be a single gene located on chromosome 16. The product encoded by this gene is unknown, but there is speculation it might code for fibrillin, one of the proteins in elastic fibers.

The usual symptoms of PXE are thickened skin with yellow bumps in localized areas and angioid streaks in front of the retina.

Diagnosis

The presence of calcium in elastic fibers, as revealed by microscopic examination of biopsied skin, unequivocally establishes PXE.

Treatment

PXE cannot be cured, but plastic surgery can treat PXE skin lesions, and laser surgery is used to prevent or slow the progression of vision loss. Excessive blood loss due to the vomiting of blood must be treated by transfusion. Mitral valve prolapse (protrusion of one or both cusps of the mitral heart valve back into the atrium during heart beating) can also be corrected by surgery, if necessary.

Alternative treatment

Some people have advocated a calcium-restricted diet, but it is not yet known whether this aids the problems brought about by PXE. It is known, however, that calcium-restriction can lead to bone disorders.

Prognosis

The prognosis is for a normal life span with a chance of circulatory problems, hypertension, gastrointestinal problems, and impaired vision. However, now that the gene for PXE has been localized, the groundwork for research to provide effective treatment has been laid. The gene probably will be cloned and sequenced, leading to the identification of the protein encoded by the PXE gene. Studying the role of this protein in elastic fibers may lead to drugs that will ameliorate or arrest the problems caused by PXE.

Prevention

There is currently no way to prevent PXE. Now that the gene responsible for PXE has been located, it is probable that genetic tests, which would provide knowledge needed to prevent cases of PXE, will become available.

There are, however, measures that can be taken to help prevent cardiovascular complications. People with PXE should control their cholesterol, blood pressure, and weight. They should exercise for cardiovascular health and to avert claudication (leg pain while walking) later in life. They should also avoid the use of tobacco, thiazide antihypertensive drugs, blood thinners like coumadin, and non-steroidal anti-inflammatory drugs like aspirin and ibuprofen. In addition, they should avoid strain, heavy lifting, and contact sports, since these activities could trigger retinal and gastrointestinal bleeding.

Key Terms

Angioid streaks

Gray, orange, or red wavy branching lines in Bruch's membrane.

Bruch's membrane

A membrane in the eye between the choroid membrane and the retina.

Connective tissue

Extracellular material that supports and binds other tissue; it consists of fibers and webs of polymers. Examples of connective tissue include bone, cartilage, and elastic fibers.

Dominant trait

A genetic trait where one copy of the gene is sufficient to yield an outward display of the trait; dominant genes mask the presence of recessive genes; dominant traits can be inherited from a single parent.

Elastic fiber

Fibrous, stretchable connective tissue made primarily from the proteins, elastin, collagen, and fibrillin.

Gene

A portion of a DNA molecule containing instructions for the development of a cell.

Mitral valve (also known as bicuspid valve)

The heart valve that prevents blood from flowing backwards from the left ventricle into the left atrium.

Recessive trait

An inherited trait that is outwardly obvious only when two copies of the gene for that trait are present --as opposed to a dominant trait, where one copy of the gene for the dominant trait is sufficient to display the trait.

Further Reading

For Your Information

Books

• Pope, F. Michael. "Pseudoxanthoma Elasticum, Cutis Laxa, and Other Disorders of Elastic Tissue." In Emery and Rimoin's Principles and Practice of Medical Genetics, 3rd. ed. edited by David L. Rimoin, J. Michael Connor, and Reed E. Pyeritz. New York: Churchill Livingstone, 1997.

  Organizations

• National Association for Pseudoxanthoma Elasticum. 1420 Ogden St., Denver, CO 80218-1910. (303) 832-5055. Fax: (303) 832-3765. derckd@ttuhsc.edu. http://www.ttuhsc.edu/pages/nape/.
• PXE International, Inc. 23 Mountain Street, Sharon, MA 02067. (617) 784-3817. PXEInter@aol.com. http://www.pxe.org/.

Gale Encyclopedia of Medicine. Gale Research, 1999.