Pseudoxanthoma elasticum

Pseudoxanthoma elasticum is a progressive disorder that is characterized by accumulated deposits of calcium (calcification) and other minerals in elastic fibers, which are a component of connective tissue. Connective tissue provides strength and flexibility to structures throughout the body.

Calcification can affect elastic fibers in the skin, eyes, and blood vessels, and less frequently in other areas such as the digestive tract. As a result, people with pseudoxanthoma elasticum may have yellowish bumps called papules on their necks, underarms, and elsewhere on the skin. They also may have changes in the eye called angioid streaks, which occur in the light-sensitive layer of cells at the back of the eye (the retina). Angioid streaks can lead to bleeding and scarring of the retina, which can cause vision loss.

Calcification of elastic fibers in the arteries can cause decreased blood flow to the arms and legs, resulting in cramping or pain with exercise (claudication). If the coronary arteries in the heart are affected, calcification can result in chest pain on exertion (angina) or rarely, a heart attack. Bleeding from blood vessels in the digestive tract may also occur.

The estimated prevalence of pseudoxanthoma elasticum ranges from 1 in 25,000 to 1 in 100,000 individuals. The true prevalence is probably higher because mildly affected people are often not diagnosed. For reasons that are unknown, this disorder is diagnosed twice as frequently in females as in males.

Mutations in the ABCC6 gene cause pseudoxanthoma elasticum.

Little is known about the function of the ABCC6 gene. It provides instructions for making a protein that transports certain substances across the cell membrane. Mutations in the ABCC6 gene lead to an absent or nonfunctional protein, which may impair the transport of substances and disrupt normal cell activities. It is unclear how ABCC6 mutations lead to the calcification of elastic fibers and the characteristic features of pseudoxanthoma elasticum.

Read more about the ABCC6 gene.

Pseudoxanthoma elasticum is inherited in an autosomal recessive manner, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

In a few cases, an affected individual has one affected parent and one parent without the signs and symptoms of the disorder. This situation is called pseudodominance because it resembles autosomal dominant inheritance, in which one copy of an altered gene in each cell is sufficient to cause a disorder. Such cases of pseudoxanthoma elasticum, however, are actually autosomal recessive because the normal-appearing parent carries an ABCC6 mutation. The affected offspring inherits two altered genes, one from each parent.