Christine O’Brien still vividly recalls the moment during her second pregnancy when a fetal scan changed everything she thought she knew about her family’s future.

“I’ll never forget the look on the radiologist’s face,” says Christine, recalling the doctor’s review of Nora’s fetal echocardiogram. “He said her arteries ‘lit up like a Christmas tree.’ She had heavy calcification throughout all of her vessels.”

In the days that followed, uncertainty turned into answers that led to the diagnosis of generalized arterial calcification of infancy (GACI) caused by ENPP1 deficiency in not only newborn Nora, but also Christine’s then 2-year-old son, Callum.

For Christine, that moment became the start of a lifelong commitment to navigating this rare genetic condition, not only for her own children, but for families around the world facing similar diagnoses. She and her husband, Michael Lemanski, teamed up with several other parents to found GACI Global, a nonprofit patient advocacy organization dedicated to supporting families affected by GACI and related conditions.

Among GACI Global’s initiatives was spearheading GACI/ARHR2 Awareness Day, which the organization began recognizing annually on Feb. 1 in 2019. The day is part of broader, ongoing efforts to increase understanding of this set of ultra-rare conditions while connecting families with each other and the medical community.

“We want people to have the right information, to give them hope and to help connect them to other families that are going through this,” says Christine, who is Co-President of GACI Global.

Navigating ENPP1 Deficiency  

ENPP1 deficiency is a rare, serious and progressive genetic condition that affects blood vessels, soft tissues and bones. The condition is associated with increased cardiovascular mortality risk across all age groups, especially in infants. Additional conditions associated with early-onset generalized arterial calcification of infancy (GACI) include ABCC6 deficiency, severe rickets and osteomalacia in children and adults. There are currently no approved treatments addressing the underlying cause of ENPP1 deficiency.

Approximately 50% of babies diagnosed with GACI die within six months of birth.

The family’s journey with ENPP1 deficiency began, unbeknownst to them, when Callum was born prematurely at just 25 weeks. As he grew, he struggled to move his shoulders and missed early motor milestones.

“He had a lot of medical mysteries that we thought were from prematurity,” Christine says. “But they really weren’t.”

Imaging revealed calcification in both shoulder joints, an unusual finding without a clear explanation. Callum underwent surgeries at 17 months and again at age 2 to remove calcified tissue. Later, imaging identified tortuous neck vessels, and he was diagnosed with Loeys‑Dietz syndrome, a rare connective tissue disorder. It was that diagnosis which prompted the fetal scan that led to both Nora and Callum being diagnosed with GACI, which a genetic test later validated was caused by ENPP1 deficiency.

“We thought if our children survived infancy, they’d be fine,” says Christine. “We had no idea that this was part of a broader disease called ENPP1 deficiency that is affecting them for their whole lifespan.”

A Journey into Advocacy  

When her children were first diagnosed, Christine struggled to find information or support.

“We left the NICU with this little yellow piece of paper with the name of the only other family in Boston facing this diagnosis,” she recalls. “It was a beacon of hope.”

Determined to connect with more families, she began searching online and reached families in Ireland, Australia, the U.K. and across the United States. When Nora was 5 months old, she reached out to another mother, Liz Molloy (now Co-President of GACI Global), and proposed creating a private Facebook support group to connect with other families.

“I didn’t want anyone to face what we faced,” Christine says reflecting on the feeling of being alone. “The roots of our advocacy organization can be traced to that.”

Hopes for the Future 

Today, Callum, now 15 years old, and Nora, 12, are finding ways to define themselves beyond their diagnosis. Callum enjoys playing the guitar and skateboarding, while Nora gravitates toward reading, writing and art. Still, they live with health complications that can be serious and limiting, such as extreme fatigue, progressive hearing loss, ongoing cardiac concerns, chronic pain and limited mobility. 

“If there were treatments available, it would be life-changing, not just in the day-to-day, but in looking to the future with more hope than we do now,” says Michael.  

Nora says she finds comfort in the fact that there are scientists researching potential medicines for her condition, as well as in the strength she has developed from navigating the challenges that living with ENPP1 deficiency present. 

“Not many of us in the world have this, and so it’s not something big that everybody is working to try to help,” Nora says. “The people that have it, we matter too.”  

“It is hard,” she adds, “but those of us that survive, we’re fighters.” 

Learn more about ENPP1 deficiency on the GACI Global website.