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 shows up most commonly in adults and sometimes in adolescents. It progresses very slowly and causes problems primarily in the skin and eyes. It can cause loose, wrinkled skin, bleeding in the eye, and leg pain when walking. Read more about PXE here.

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 may develop loose and wrinkly skin. This occurs in the flexor areas: neck, under the arms, in the groin, and behind the knees.

Eye

Some patients may be at risk of developing angioid streaks. These are cracks in Bruch’s membrane which separate the outer layer of the retina from the blood vessels beneath. This can lead to retinal bleeding.

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.

GI

Gastrointestinal issues, including gastrointestinal hemorrhage, occurs in approximately 13% of patients.  This occurs due to degeneration of arterial elastic fibers in the mucosa of the stomach and intestine.