Still inside the womb, the toothpick-thin arteries in the baby girl’s heart were already clogging with calcium. Grimly, her parents knew all too well that it was a death sentence; they had been through this terrible diagnosis twice before.
It was January 2013. From the family farmhouse in Minnesota, Anne and Jerry Van Wyk looked out at the snowy countryside. The month following the diagnosis at Anne’s 20-week ultrasound had been a numb darkness harking back to painful memories.
Their first child, Reid, born in 2001, had been diagnosed with generalized arterial calcification of infancy (GACI), a rare disease that blocks arteries throughout the body, impairing blood flow to the heart and brain. He lived for only seven weeks. Anne and Jerry learned that they each carried a recessive gene for GACI, meaning any child they bore would have a one in four chance of having the disease.
After their excruciating loss, the couple was blessed with three healthy children: big brother Drew and twins Julia and Graham. Anne was pregnant next in 2010 when the cruel math of genetics shattered their lives again. Their son Ian lived for only five weeks before his heart failed due to complications from GACI.
Now here they were once more. “How are we going to do this again?” they wondered.
Searching for answers
Jerry put Google through its paces, pouring over information on every children’s hospital and research center in North America. An idea began to crystallize.
“Our doctors weren’t able to try to treat Reid and Ian until after they were born,” says Jerry. “And by then it was too late. So we thought, maybe we can do something in utero?”
He found a few dozen places with prenatal treatment centers. Of those, only a handful had extensive experience with fetal heart conditions. And of those, only one boasted expertise in rare genetic conditions: The Children’s Hospital of Philadelphia.
Developing a unique in utero solution
They made the 20-hour drive from Minnesota. “From the moment we arrived, we knew we were in the right place,” says Anne.
They met with cardiologist David Goldberg, MD, who is a member of the Fetal Heart Program team, as well as Juan Martinez-Poyer, MD, of the Center for Fetal Diagnosis and Treatment. Such a complex case would require collaboration across several disciplines. They added to the team Michael Levine, MD, chief of the Division of Endocrinology and Diabetes and the Lester Baker Endowed Chair in Pediatric Diabetes. Levine had led a team that identified a gene that causes GACI and is one of the few physician-scientists in the world with deep expertise in the disease.
Knowing the baby would die without intervention, the team put their heads together and devised an experimental treatment. “GACI inhibits a protein that keeps calcium from building up in arteries,” says Levine. “So we thought, 'Is there a way to replace that protein?'”
Levine knew about an osteoporosis drug called etidronate, which is rarely used because it blocks the calcification of bones. But because it has a chemical structure resembling the protein missing from the Van Wyks’ developing baby, Levine proposed giving it to Anne. The treatment was unprecedented, but there was no better option. The Van Wyks agreed to proceed with the plan.
It worked. Follow-up scans of the fetus showed a halt to the progressive clogging of the baby’s arteries.
Reversing calcification after birth
On April 8, 2013, Natalie Grace Van Wyk was born in the Garbose Family Special Delivery Unit at CHOP. But she wasn’t out of the woods.
“We had already seen calcium deposits in her arteries,” says Goldberg. “We had to try to reverse the process. Having such a diverse team — experts from cardiology, endocrinology and fetal medicine — helped us to come up with a creative treatment plan.”
They began infusions of sodium thiosulfate (STS), a powerful medication sometimes used to treat calcium buildup in the arteries of adults with kidney failure. It was more uncharted territory, as STS had never been given to such a young baby, nor had it been used for GACI.
Natalie’s heart underwent scan after scan. “Each week we were all white knuckles waiting for the report on how she was doing,” says Jerry.
Thankfully, the calcifications in her arteries began to recede. Her heart was healing.
In May 2014, Natalie had her last STS infusion. Scans did not detect any calcium in the coronary arteries of her heart, and the calcium in her other blood vessels appeared to be significantly reduced. Her blood work and heart function remained strong, and she was growing and developing normally.
Today, Natalie is a spunky, healthy 18-month-old. She's fun, interactive and getting into everything. You’d never know she is a medical miracle.
“We came to CHOP because we believed that if something could be done for Natalie, it could be done here,” says Anne. “There were so many reasons to lose hope, but when it comes to taking care of your children, there’s no room for regrets.”
— Mark Turbiville