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ABCC6 Deficiency is a rare, inherited, genetic inborn error of metabolism caused by mutations in the ABCC6 gene. It is estimated that there more than 67,000 individuals worldwide with this systemic and progressively debilitating condition. ABCC6 Deficiency is inherited as a recessive trait in which the genetic mutations result in decreased or absent activity of the ABCC6 protein. The Deficiency leads to low plasma levels of PPi and is associated with pathological mineralization in blood vessels and soft tissues throughout the body, resulting in significant morbidity, including blindness, life-threatening cardiovascular complications, and skin calcification. The pathological mineralization associated with ABCC6 Deficiency is the result of ectopic calcification in elastic fibers, a component of connective tissue, which provides strength and flexibility to structures throughout the body. Ectopic calcification can affect function in elastic fibers in the eyes, blood vessels, and skin, and less frequently in other areas such as the digestive tract.
Some infants with ABCC6 Deficiency are diagnosed with a vascular calcification condition resembling the acute infantile form of ENPP1 Deficiency. In older patients, ABCC6 Deficiency presents as pseudoxanthoma elasticum, or PXE, a rare disorder in which individuals develop calcification of soft connective tissues, including in the eyes, cardiovascular system, and skin.
Individuals with PXE often have abnormalities in the eyes, such as a change in the pigmented cells of the retina or angioid streaks that occur when tiny cracks form in Bruch’s membrane, the elastic membrane beneath the retina. Choroidal neovascularization — subsequent bleeding and scarring of the retina — may also occur, which, together with the damage to Bruch’s membrane, can cause vision loss. A recent report stated that 37 percent of PXE patients over the age of 50 experienced visual impairment and 15 percent were legally blind.1 Pathological mineralization of the vessels that carry blood from the heart to the rest of the body may cause other signs and symptoms of PXE. Ectopic calcification narrows blood vessels, particularly in the lower extremities, and leads to claudication, a condition characterized by cramping and pain during exercise due to decreased blood flow to the arms and legs. Individuals with PXE may also have yellowish bumps called papules on the neck, underarms, and other areas of the skin surrounding the joints. These papules are painful, can impair joint movement, and indicate a general, systemic, pathological process of soft tissue calcification.
- Risseeuw S, Ossewaarde-van Norel J, Klayer CCW, Colijn JM, Imhof SM, van Leeuwen R. Visual acuity in pseudoxanthoma elasticum. Retina. 2019;39(8):1580-1587.