Surreal illustration symbolizing calcification in PXE.

PXE: Unlocking the Mystery of This Rare Genetic Disorder

Samir D’Costa in Health & Wellness August 2025 • 4 min read.

"A breakthrough in understanding pseudoxanthoma elasticum (PXE) reveals new possibilities for treatment."

Since the early 1900s, when the concept of inborn errors of metabolism was first introduced, scientists have identified and characterized countless metabolic diseases. However, some conditions remain stubbornly resistant to understanding. Pseudoxanthoma elasticum (PXE), a relatively frequent genetic disorder characterized by abnormal calcification in the skin, eyes, and blood vessels, was one such enigma until very recently.

In 2013, researchers finally identified the cause of PXE: a malfunction in a specific biochemical mechanism. This discovery not only shed light on the disease's origins but also opened up potential avenues for new treatments. What makes this particularly exciting is that, until now, PXE has remained largely untreatable.

This article explores the complex journey that led to our current understanding of PXE. We'll break down the key biochemical processes involved, discuss some of the controversies surrounding the condition, and highlight promising new treatment strategies.

What is PXE, and What are the Symptoms?

Surreal illustration symbolizing calcification in PXE.

PXE is a genetic disorder that leads to abnormal calcification throughout the body. This calcification most notably affects the skin, blood vessels, and eyes. The root cause is the buildup of amorphous calcium phosphate, which gradually transforms into hydroxyapatite.

While the disease progresses slowly, its clinical course can vary significantly from person to person. Some individuals may not experience vision problems or cardiovascular issues until they are well into their 60s. In rare instances, infants can experience rapid calcification and cardiac arrest. Unfortunately, previous attempts to slow the disease through diet or medication have largely been unsuccessful.

Autosomal Recessive: PXE is an inherited condition, meaning both parents must carry the faulty gene for a child to be affected.
Frequency: It is estimated to affect 1 in 50,000 people.
Gene Defect: The primary cause lies in mutations of the ABCC6 gene. This gene is responsible for producing a protein called multidrug resistance protein 6 (MRP6), now known as ABCC6.
The ABCC6 Paradox: ABCC6 is mainly found in the liver and kidneys, which raises the question: how can a defect in a liver/kidney protein cause calcification in other parts of the body? This question has fueled debate and research in the field.

One theory suggests that a small amount of ABCC6 exists in peripheral tissues and directly prevents calcification. Another, more widely accepted theory, is that PXE is a metabolic disorder. In this view, ABCC6 in the liver is responsible for secreting a substance into the bloodstream that prevents calcification throughout the body.

Hope for the Future

The discovery of the link between ABCC6, ATP, and PP opens exciting possibilities for treating PXE. Supplementing PP directly or finding ways to increase its levels in the body are now active areas of research.

Animal studies have shown promising results with PP supplementation, delaying the onset of calcification. Early-generation bisphosphonates, relatively inexpensive drugs originally developed for other conditions, are also being explored as potential treatments.

These new treatment initiatives for PXE could offer insights and approaches that benefit other disorders of calcium phosphate metabolism, offering hope for a wider range of patients.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.tibs.2018.10.005, Alternate LINK

Title: Pxe, A Mysterious Inborn Error Clarified

Subject: Molecular Biology

Journal: Trends in Biochemical Sciences

Publisher: Elsevier BV

Authors: Piet Borst, András Váradi, Koen Van De Wetering

Published: 2019-02-01

Everything You Need To Know

What is pseudoxanthoma elasticum (PXE), and how does it affect the body?

Pseudoxanthoma elasticum, or PXE, is a genetic disorder characterized by abnormal calcification in the body, primarily affecting the skin, eyes, and blood vessels. This calcification results from the buildup of amorphous calcium phosphate, which transforms into hydroxyapatite over time. Although PXE progresses slowly, the severity and onset of symptoms can vary greatly among individuals, ranging from vision problems and cardiovascular issues later in life to rare instances of rapid calcification and cardiac arrest in infants.

What role does the ABCC6 gene play in pseudoxanthoma elasticum (PXE)?

Mutations in the ABCC6 gene are the primary cause of pseudoxanthoma elasticum (PXE). This gene is responsible for producing the multidrug resistance protein 6, now known as ABCC6. Although ABCC6 is mainly found in the liver and kidneys, its malfunction leads to calcification in other parts of the body. The prevailing theory suggests that ABCC6 in the liver secretes a substance into the bloodstream, preventing calcification throughout the body. Therefore, a defect in ABCC6 disrupts this process, resulting in the symptoms observed in pseudoxanthoma elasticum.

How is pseudoxanthoma elasticum (PXE) inherited, and what is its frequency in the population?

Pseudoxanthoma elasticum (PXE) is inherited as an autosomal recessive condition, meaning that both parents must carry the faulty gene for a child to be affected. It is estimated to affect 1 in 50,000 people. Understanding the inheritance pattern is crucial for genetic counseling and family planning, particularly for individuals with a family history of pseudoxanthoma elasticum.

What are the current research efforts focused on for treating pseudoxanthoma elasticum (PXE), and how does ATP play a role?

Current research efforts for treating pseudoxanthoma elasticum (PXE) are focused on supplementing PP directly or finding ways to increase its levels in the body. The discovery of the link between ABCC6, ATP, and PP has opened exciting possibilities for treatment. While the role of ATP is not explicitly detailed, this research indicates a metabolic pathway involving ABCC6 that needs to be better understood to improve levels of PP. This represents a significant shift from previous largely unsuccessful attempts to slow pseudoxanthoma elasticum through diet or medication.

The ABCC6 gene is predominantly found in the liver and kidneys, yet pseudoxanthoma elasticum (PXE) affects the skin, eyes, and blood vessels. How do scientists explain this apparent paradox?

The paradox of how a defect in the ABCC6 gene, primarily found in the liver and kidneys, causes calcification in the skin, eyes, and blood vessels in pseudoxanthoma elasticum (PXE) is explained by two main theories. One suggests that a small amount of ABCC6 exists in peripheral tissues and directly prevents calcification. The more widely accepted theory is that pseudoxanthoma elasticum is a metabolic disorder. In this view, ABCC6 in the liver is responsible for secreting a substance into the bloodstream that prevents calcification throughout the body. Thus, a malfunction in ABCC6 disrupts this systemic protective mechanism, leading to calcification in affected tissues.