Generalized Arterial Calcification of Infancy

Generalized arterial calcification of infancy (GACI) is an extremely rare genetic disorder. It is caused by mutations in the ENPP1 gene in 75% of the subjects or in mutations in the ABCC6 genes in 10% of patients. However, sometimes individuals affected with GACI do not have mutations in the ENPP1 or ABCC6 gene and in those cases the cause of the disorder is unknown.The condition usually affects infants during the first 6 months of life. This condition is inherited as an autosomal recessive pattern. It is characterized by generalized calcification of the arterial internal elastic lamina, leading to rupture of the lamina and occlusive changes in the tunica intima with stenosis and decreased elasticity of the vessel wall. Unfortunately, many infants die of vaso-occlusive disease, especially of the coronary arteries.There are 2 forms of GACI that can be indicated on a genetic test:
GACI Type 1 is caused by mutations in the ENPP1 gene. It is called ENPP1 Deficiency. Patients with the ENPP1 Deficiency are at risk of developing Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2). ARHR2 can cause weakening in the bones, pain in bones and joints bone deformities (knocked knees, bowed legs), dental problems, calcification of ligaments and short stature. With proper treatment the bones can be strengthened and side effects minimized.GACI Type 2 is caused by mutations in the ABCC6 gene. It is called ABCC6 Deficiency. As children affected by GACI due to ABCC6 Deficiency get older, they can develop characteristics similar to pseudoxanthoma elasticum (PXE). This condition affects the elastic tissue of the skin, the eye, cardiovascular and gastrointestinal systems.