What is Pseudoxanthoma Elasticum?

Pseudoxanthoma elasticum, also called PXE, is an inherited genetic disorder which causes fibers in certain tissues to undergo a process of calcification and fragmentation. These processes can cause serious side effects including vision loss, decreased blood flow to limbs, and rarely, coronary problems. Treatment cannot prevent calcification from occurring but some medications can help prevent vision loss.

The underlying cause of pseudoxanthoma elasticum is a mutation in a gene called ABCC6. This gene codes for a protein involves in transportation of substances across the cell membrane. While the exact function of the protein is not known, the fact that it is a transporter protein suggests that the disease is metabolic in nature. One theory is that PXE results in an accumulation of one or more metabolites due to the inactivity of the transporter, and this accumulation somehow results in calcification in certain tissue types.

People who are born with pseudoxanthoma elasticum do not always show symptoms during childhood. In most people with this disorder, symptoms begin to appear during adolescence or adulthood. The earliest symptom of pseudoxanthoma elasticum is the development of small papules on the neck and groin and the insides of the knees and elbows.

As the disease progresses, the retina of the eye becomes affected by calcification of membrane fibers. This causes the development of cracks in the Bruch membrane, which separates retinal layers in the eye. While these cracks themselves do not damage the eye, they can cause small blood vessels in the retina to hemorrhage. These retina hemorrhages are what lead to vision loss.

Loss of central vision is one of the most serious and most prevalent problems that people with PXE face, but is not the only issue. People affected by pseudoxanthoma elasticum may also have cardiovascular or gastrointestinal symptoms. These occur when elastin fibers in blood vessels become calcified.

Possible symptoms of gastrointestinal involvement include blood in the stool, vomiting blood, and gastrointestinal hemorrhage. If the cardiovascular system is affected, angina and high blood pressure may occur. In very rare cases cardiovascular involvement may cause a heart attack. Calcification of blood vessels and arteries can also reduce blood flow to the limbs. This can cause cramping, and may also cause pain during exercise.

Most of the calcification that occurs as a result of PXE can not be reversed, but some of the damage can be treated or prevented as long as diagnosis is made early enough. Skin lesions can be removed via surgery if desired, although this is a mostly cosmetic treatment. Cardiovascular symptoms are treated with exercise and a diet low in fat and calcium, although the link between dietary calcium and PXE prognosis is not confirmed.

Prevention of retinal hemorrhages is one of the most pressing concerns in pseudoxanthoma elasticum. Regular retinal screening is used to monitor the progress of the disease, and laser coagulation is used to help minimize the extent of vision loss. Patients are often advised to take supplementary zinc, as well as vitamins A, C, and E, to reduce hemorrhage risks.