Generalized Arterial Calcification of Infancy (GACI)

What Is GACI? 

GACI is a rare inherited condition that affects about 1 in 64,000 people. It causes too much calcium to build up in blood vessels and other tissues like the heart valves, joints, and tendons.

• Signs are often found before birth or in early infancy.
• About half of affected babies do not survive past 6 months, but for those who do, calcium buildup can improve over time.

What Causes GACI?

GACI can happen when certain genes don’t work as they should:

• ENPP1 deficiency (GACI type 1): Most common cause (about 2/3 of cases). ENPP1 helps produce substances that prevent calcium buildup. Without enough ENPP1 activity, calcium can collect in blood vessel walls.
• ABCC6 deficiency (GACI type 2): Causes similar problems and accounts for about 15% of cases.
• In about 15% of people with GACI, the cause is unknown.

Some children with ENPP1 deficiency may also develop a bone condition called autosomal recessive hypophosphatemic rickets type 2 (ARHR2) later in infancy or childhood, even if they never had GACI as a baby.

What Are Signs & Symptoms of GACI? 

Symptoms can vary widely, even among family members. Common issues include:

Heart & Blood Vessels:

• Breathing problems
• Heart failure or “heart attack” (myocardial infarction)
• High blood pressure
• Calcium buildup in arteries

Growth & Feeding:

• Trouble feeding and gaining weight
• Short height
• Fatigue or low energy

Bone & Joint Problems (often seen with ENPP1-related ARHR2):

• Bowed legs or knock knees
• Bone pain
• Abnormal growth plates (rickets) on x-ray
• Cervical spine fusion (neck bones fused)
• Calcification where tendons and ligaments attach to bone
• Early skull bone fusion (craniosynostosis)
• Dental issues

Other:

• Hearing loss
• Gastrointestinal issues

How Is GACI Diagnosed?

• Genetic testing can confirm ENPP1 or ABCC6 gene changes.
• Blood and urine tests can check phosphorus and related levels.
• Imaging tests (like ultrasound, x-ray) can look for calcium buildup or bone changes.
• If ENPP1 deficiency is found early, providers can monitor for ARHR2 before bone deformities appear.

How Is GACI Treated?

There is no cure yet, but treatment can help manage symptoms and reduce complications.

For Infants with GACI:

• Medicines such as sodium thiosulfate or bisphosphonates (most helpful if started in the first week of life)
• Treatments focused on specific arteries or organs affected

For Children with ARHR2:

• Phosphorus and active vitamin D supplements
• Monitoring for side effects such as stomach upset, diarrhea, or calcium buildup in the kidneys (regular kidney ultrasounds)
• Surgery may be considered to correct severe bone deformities

Ongoing Research:

• Clinical trials are testing medicines to replace the missing ENPP1 enzyme.

What to Expect with Our Care Team 

If GACI is suspected or diagnosed:

• We can arrange genetic testing for ENPP1 and ABCC6.
• We’ll monitor your child’s blood, urine, and imaging studies over time.
• Our team will develop a personalized treatment plan based on your child’s symptoms and needs.
• Care is often coordinated with specialists in nephrology, cardiology, pulmonology, and audiology.

Additional Resources 

• GACI Global