ABCC6 Deficiency

ABCC6 Deficiency is caused by mutations in the ABCC6 gene which causes low levels of pyrophosphate (PPi) and adenosine in the blood.  Infants with ABCC6 Deficiency may present with Generalized Arterial Calcification (GACI) Type 2.  This condition resembles GACI Type 1, the infant form of ENPP1 Deficiency.  In older individuals, ABCC6 Deficiency presents as pseudoxanthoma elasticum (PXE), which is characterized by pathological mineralization in blood vessels and soft tissues, clinically affecting the skin, eyes, and vascular system.

MANIFESTATIONS OF ABCC6 DEFICIENCY

Generalized Arterial Calcification of Infancy

The acute infantile phase, GACI, is characterized by calcification of large and medium-sized arteries, along with neointimal proliferation.  This causes narrowing of the vessels and reduced blood flow, which can result in dysfunction and potential failure of major organs.  Read more about GACI here.

Approximately 50% of babies born with GACI do not survive past 6 months of age.

Pseudoxanthoma Elasticum

PXE is a slow-progressing calcification disorder which affects connective tissue. It can affect the skin, eyes, gastrointestinal and cardiovascular systems. Calcium can be deposited in soft tissues which can lead to skin lesions, retinal abnormalities, and vascular calcification.

The disease prevalence is 1:25,000 to 1:50,000.

COMPLICATIONS OF ABCC6 DEFICIENCY

Cardiovascular

Cardiac symptoms in infants can include: calcification of arteries and heart valves, narrowing of blood vessels, high blood pressure, heart attack, and stroke. Approximately 50% of adult patients develop peripheral artery disease.

Skin

Some patients go on to develop pseudoxanthoma elasticum (PXE) which is when calcium is deposited in the skin. It frequently occurs on the neck, underarms, or other areas of skin that touch when a joint bends.

Eye

Some patients may be at risk for developing Angioid streaks in the eyes. These are small breaks in Bruch’s Membrane, an elastic tissue containing the membrane of the retina, that may become calcified and crack.

GI

PXE can cause gastrointestinal hemorrhage in approximately 13% of patients.  This occurs due to degeneration of arterial elastic fibers in the mucosa of the stomach and intestine.

Neurological

Neurological issues and developmental delays present in approximately 50% of patients with GACI Type 2. Strokes occur in some patients as a result of calcification and stenosis in the intracranial arteries.

Joints

Joint calcification is seen in approximately 25% of babies born with GACI Type 2.