Generalized Arterial Calcification of Infancy (GACI)

What is generalized arterial calcification of infancy?

Generalized arterial calcification of infancy (GACI) is a rare genetic disorder that is characterized by abnormal buildup of calcium in the artery walls. It was first named GACI in 2003; however, the condition itself was first described in 1899. Since then, 200 cases have been reported in medical literature.

What are the symptoms of generalized arterial calcification of infancy?

Symptoms of this condition may differ depending on the age of the affected individual, and not every patient will experience every symptom. For example, newborns present with reduced/absent pulses, difficulty breathing, fluid accumulation in the extremities, cardiomyopathy, high blood pressure, heart failure, irritability, failure to thrive, and feeding difficulties.

In other cases, children will not present with symptoms (which are typically gradual or persistent) until they are between the ages of three and six. They can experience the same symptoms as newborns, alongside vascular disease, narrowing of the arteries, congestive heart failure, plaque build-up, gastrointestinal complications, joint calcifications, and restricted blood flow. Rare symptoms include cervical spine fusion, hearing loss, rickets, pseudoxanthoma elasticum (PXE), and dental issues.

What causes generalized arterial calcification of infancy?

Two genetic mutations are responsible for the two different forms of GACI: ABCC6 and ENPP1. Type 1 is caused by an altered ENPP1 gene, whereas type 2 is the result of a mutated ABCC6 gene. Both of these mutations cause a lack of pyrophosphate in the blood, which then impacts calcium regulation. Therefore, calcium is able to accumulate in the blood vessels and cause the characteristic symptoms of the disease.

How is generalized arterial calcification of infancy diagnosed?

In about half of cases, doctors will notice the characteristic symptoms of GACI soon after birth and diagnose it promptly. In other cases, this diagnosis does not occur until a child is between the ages of three and six. However, some cases are also diagnosed before birth via ultrasound and genetic testing.

In the remaining cases, the characteristic symptoms paired with certain tests (blood tests, imaging tests, etc.) are required to diagnose GACI.

What are the treatments for generalized arterial calcification of infancy?

There is no cure for this condition, but there are medications and procedures used to combat the calcium accumulation. Options include bisphosphonates, sodium thiosulfate (STS), and heart transplants. Otherwise, treatment is symptomatic and typically requires a multidisciplinary team.