Generalized
arterial calcification of infancy (
GACI) is an autosomal recessive disorder caused by mutations in the ENPP1 gene. It is characterized by mineralization of the arterial blood vessels, often diagnosed prenatally, and associated with death in early childhood. There is no effective treatment for this devastating disorder. We previously characterized the Enpp1asjmutant mouse as a model of
GACI, and we have now explored the effect of elevated dietary
magnesium (five-fold) in pregnant mothers and continuing for the first 14 weeks of postnatal life. The mothers were kept on either control diet or experimental diet supplemented with
magnesium. Upon weaning at 4 weeks of age the pups were placed either on control diet or high
magnesium diet. The degree of mineralization was assessed at 14 weeks of age by histopathology and a chemical
calcium assay in muzzle skin, kidney and aorta. Mice placed on high
magnesium diet showed little, if any, evidence of mineralization when their corresponding mothers were also placed on diet enriched with
magnesium during pregnancy and nursing. The reduced ectopic mineralization in these mice was accompanied by increased
calcium and
magnesium content in the urine, suggesting that
magnesium competes
calcium-phosphate binding thereby preventing the
mineral deposition. These results have implications for dietary management of pregnancies in which the fetus is suspected of having
GACI. Moreover, augmenting a diet with high
magnesium may be beneficial for other ectopic mineralization diseases, including
nephrocalcinosis.