What causes ABCC6 Deficiency?

People with ABCC6 Deficiency have one or two ABCC6 gene variants, which suppresses the body’s ability to produce enough of a protein called ABCC6. ABCC6 Deficiency affects the PPi-Adenosine Pathway by reducing the levels of circulating ATP (adenosine triphosphate) – which is used to generate PPi and adenosine. In ABCC6 Deficiency, the body develops mineral build-up in elastic tissue in the eyes, skin, and vasculature due to low levels of PPi. The body may also have blood vessel narrowing and difficulty maintaining blood vessel health due to low levels of adenosine.

ABCC6 Deficiency is caused by mutation(s) in the ABCC6 gene, leading to reduced extracellular ATP
This leads to low levels of pyrophosphate (PPi) a key inhibitor of bone mineral (hydroxyapatite) formation and deposition
Left unchecked, hydroxyapatite deposits into the soft tissues including the blood vessels, skin, and eyes. This is known as ectopic calcification.
ABCC6 Deficiency is also associated with intimal proliferation which leads to narrowing and obstruction of blood vessels

Living with ABCC6 Deficiency

The symptoms of ABCC6 Deficiency may vary from person to person and the condition can affect people of all ages. The signs and symptoms of the disease may vary in terms of severity, even among people in the same family. Symptoms can continue long-term, and they may even worsen over time.

People with ABCC6 Deficiency can suffer from a host of complications shortly after birth, in their childhood, and through adulthood. Learn more about the three forms of this disorder:

GACI Type 2 – Infant
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ABCC6 Deficiency – Child
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PXE – Adult
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Cardiovascular
Heart failure, severe hypertension, cardiomyoapaty, heart valve defects, myocardial infarction
Cardiovascular
Heart failure, hypertension, heart attack, respiratory distress, heart valve defect
Cardiovascular
Heart failure, hypertension, respiratory distress, heart valve defect 
Cardiovascular
Peripheral artery disease, hypertension
Neurologic
Neurologic
Ischemic stroke, seizure, cognitive or developmental delay
Neurologic
Ischemic stroke, seizure, migraine, cognitive or developmental delay
Neurologic
Ischemic stroke
 Ocular
Ocular
vision impairment or vision loss
Ocular
Vision loss or blindness
Dermatologic
Dermatologic
Papules and plaques
Dermatologic
Papules, plaques, loose or sagging skin
GACI Type 2 – Generalized Arterial Calcification of Infancy Type 2

Some infants with ABCC6 Deficiency have serious cardiovascular or neurovascular problems shortly after birth due to calcification buildup or narrowing of blood vessels. This calcification makes the arteries stiff and narrow, which can make it hard for blood to flow properly. As a result, babies with GACI Type-2 may have problems affecting their, heart, brain, and other organs because the organs cannot get enough oxygen-rich blood. GACI Type-2 can cause symptoms like heart failure, high blood pressure, breathing difficulties, stroke or seizure, or failure to thrive. Infants with GACI Type-2 have a poor prognosis, with approximately 10% mortality before the age of 6 months despite supportive care.

Children with ABCC6 Deficiency

Children with ABCC6 Deficiency may experience neurological problems due to cerebrovascular stenosis and calcification – which impedes blood flow to the brain. Patients may experience seizure or stroke which can lead to significant disability, including paralysis, vision impairment or vision loss, and problems with speech or movement. Some children may also have severe cardiovascular problems due to stenosis and calcification in their arteries.

ABCC6 Pediatric Story
PXE – Pseudoxanthoma Elasticum

ABCC6 Deficiency is more commonly known as PXE, which is characterized by abnormalities such as wrinkled and leathery skin, yellowish bumps on the skin (pseudoxanthomas), and calcification in the retina of the eyes that can cause severe vision problems, leading to blindness in some cases. Additionally, there can be calcification and narrowing of blood vessels, which can increase the risk of vascular complications such as cardiovascular disease, peripheral arterial disease, and stroke.

Disease prevalence

1:25,000 to 1:50,000

How does INZ-701 work in ABCC6 Deficiency?

INZ-701 is an ENPP1 enzyme replacement therapy (ERT) given as an injection under the skin (called a subcutaneous injection) that is designed to increase PPi and adenosine in the body to help improve or prevent symptoms of ABCC6 Deficiency.

INZ-701 is an investigational product and that has not yet been approved by the U.S. Food and Drug Administration or any other health regulatory authority.

 

Join a Clinical Trial

We are enrolling infants and pediatric patients with ABCC6 Deficiency in clinical trials for a potential new treatment. Your child’s participation can help us better understand this disease, evaluate the safety and efficacy of INZ-701, and inform future treatment options.

ABCC6 Deficiency Trials