Can mineral content in diet influence mineralization in Pseudoxanthoma Elasticum ( PXE ) ?

Content Provider	Semantic Scholar
Author	Duvall, Eliza
Copyright Year	2016
Abstract	Pseudoxanthoma Elasticum (PXE) is a rare genetic disorder with no effective treatment. The usual signs and symptoms of the disease are skin lesions, vision loss, and/or cardiovascular complications as a result of mineralization. Environment and lifestyle, including diet, influence health; this report examines potential effects of mineral content (calcium, vitamin K, magnesium, or zinc plus antioxidants) in diet on the signs and symptoms of PXE in animal models and a few human studies between 1984 to 2016. Calcium: A paper published long ago wrongly asserted that reducing calcium intake in people affected by PXE lessened the severity of PXE. Abcc6 mouse models (mice that have been given the same genetic mutations as people with PXE) show no correlation between calcium intake and the severity of the condition. Vitamin K: No correlation has been found between vitamin K intake and mineralization in mouse models. However, in zebrafish an increase of vitamin K has completely eliminated mineralization on the skeleton. Magnesium: Diets with high amounts of magnesium result in a reduction or elimination of mineralization in Abcc6 mice and a decrease in magnesium has the opposite effect. A clinical trial was completed in 2015 examining the effects of magnesium content in people affected by PXE. The results are not yet published. Other minerals: Similarities between Age-Related Macular Degeneration (AMD) and PXE related vision loss might offer some insight into PXE. AMD progression slows with an increase of zinc plus antioxidants. Clinical trials and Abcc6 mouse models suggest mineral content in diet modifies PXE symptoms, however, there are no conclusive results. Introduction Pseudoxanthoma Elasticum (PXE) is a rare heritable disorder affecting as many as 1 in 25,0000 people. PXE is caused by a mutation in the ABCC6 gene located on chromosome 16; more than 300 mutations are known. Even when people have the same mutation, their clinical signs and symptoms are often different. Common signs of PXE include [1] mineralization of the middle layer of the skin, leading to bumps and loose skin, [2] deterioration of the membrane beneath the retinal Bruch’s membrane from mineralizing tissues lead to loss of central vision, and [3] obstruction of small and medium sized arteries resulting in cardiovascular complications such as claudication or cramping in calves or early manifestations of heart disease. PXE patients demonstrate a variety of symptoms and severity all caused by mineralization. The different signs symptoms from person to person suggests other factors contribute to PXE manifestations, including environment, lifestyle, or diet. Mouse models, zebrafish, PXE clinical trials, and Age-Related Macular Degeneration (AMD) clinical trials suggests mineral content can modify the severity of PXE. This report examines research publications on calcium, vitamin K, magnesium, and zinc plus antioxidants on the severity of PXE symptoms. PXE advancements have been made through knock out mouse models. These Abcc6 mice replicate genetic and structural features of humans with PXE. The mice demonstrate mineralization in connective tissues of the skin, eyes, and arterial blood vessels, as seen in people affected by PXE. Unlike humans, mice have a biomarker in the area around their whiskers that show at 5-6 weeks of age, reflecting inactive Abcc6. The degree of mineralization at this location and in the blood vessels can be measured quantitatively. This data reflects how influential a factor is, such as mineral content in diet. Humans do not have a clear biomarker to measure influential factors, which challenges PXE research. Studies on AMD give insight to PXE related vision loss. AMD is the leading cause of blindness among people over the age of 50 and is similar to PXE. Drusens are deposits formed between two areas of the eye as AMD advances. These areas are the retinal pigmented epithelium (RPE) and Bruch’s Membrane. PXE related vision loss is due to cracks in Bruch’s membrane, known as angioid streaks. Central vision loss in AMD and PXE appears blurry, distorted, or dark and may worsen over time due to mineral build up. Many studies have been conducted to better understand the cause and progression of AMD because it’s a common eye condition. These studies provide insight on what’s happening with people’s vision who are affected by PXE. Methods Consumption of calcium, vitamin K, magnesium, and zinc plus antioxidants all play a role in the human body. This report focuses on published research from 1984-2016 on these four minerals to determine the effects on people with PXE. The studies reviewed are electronic, published papers found on PubMed. Other information on mineral mechanisms was discovered in a video lecture on bone mineralization or the National Institute of Health’s website.
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Alternate Webpage(s)	https://www.pxe.org/sites/default/files/Nutrition%20content_PXE%20LAB.pdf
Language	English
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Content Type	Text
Resource Type	Article