Which are the causes of Pseudoxanthoma Elasticum (PXE)?

Pseudoxanthoma Elasticum (PXE) is a rare genetic disorder that affects the connective tissues in the body, particularly the skin, eyes, and blood vessels. It is characterized by the progressive calcification and fragmentation of elastic fibers, leading to various symptoms and complications.

1. Genetic Mutations: The primary cause of PXE is mutations in the ABCC6 gene, which provides instructions for producing a protein called ATP-binding cassette subfamily C member 6. This protein is responsible for transporting certain molecules across cell membranes. Mutations in the ABCC6 gene disrupt the normal functioning of the protein, leading to the accumulation of calcium and other minerals in the elastic fibers.

2. Inheritance: PXE is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated ABCC6 gene (one from each parent) to develop the disorder. If both parents carry a single copy of the mutated gene, each of their children has a 25% chance of inheriting two copies and developing PXE.

3. Genetic Variability: The severity and progression of PXE can vary widely among affected individuals, even within the same family. This variability is thought to be influenced by other genetic and environmental factors that modify the expression of the ABCC6 gene.

4. Unknown Factors: While the genetic cause of PXE is well-established, the exact mechanisms by which the ABCC6 gene mutations lead to elastic fiber calcification are still not fully understood. It is believed that the abnormal mineralization process involves interactions between the mutated protein and other molecules in the extracellular matrix.

5. Age and Gender: PXE symptoms typically begin to manifest during childhood or adolescence, although they can appear later in life. The disorder affects both males and females equally.

6. Other Risk Factors: Some studies suggest that certain factors, such as smoking and high levels of vitamin K intake, may influence the severity of PXE symptoms. However, more research is needed to establish a definitive link between these factors and the development of the disorder.

While there is currently no cure for PXE, early diagnosis and management of symptoms can help improve the quality of life for affected individuals. Regular monitoring by healthcare professionals and appropriate interventions can help address specific complications associated with PXE, such as vision problems, cardiovascular issues, and skin abnormalities.