Our Journey with GM3 – the Rarest of Rare Diseases .

Children's Hospital Los Angeles

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Despite the lobby’s mid-morning bustle, Connor Mast slept soundly in his stroller as his mother, Crystal talked, her voice tender but sturdy, “We had felt like our family was finished with Jordan but I got pregnant and Connor came. We were a bit fearful because we knew that the percentage was high to have another child with GM3.”

Connor underwent genetic testing four days after his birth and it was confirmed, results showed that Connor had GM3 synthase deficiency. This rare disease, with only 100 reported patients currently is a challenge to diagnose just because of how rare it truly is. Most reported cases are from Old Order Amish communities, and with Connor’s birth, his family accounts for two of the reported cases.

Affected infants become irritable and develop feeding and vomiting issues. Recurrent seizures and problems with brain development follow. GM3 synthase deficiency hinders the chemical reaction that is the first step in the production of gangliosides, molecules that appear to be important for brain development and function.

Connor’s family already lost their son Jordan to GM3, but his journey, his death, gave Connor a fighting chance against his GM3 deficiency. Crystal firmly believes that “Jordan really gave Connor life,” and in a very possible way, others as well.

Big brother, leading the way

“Jordan needed around the clock care,” Crystal recalls. “He started screaming at about 2 weeks and this would go on for nearly two years. I had a hard time finding a doctor that would take his illness serious.”

At 3 months old, Jordan was hospitalized and underwent intense testing. He wasn’t eating so a G-tube was inserted through his abdomen to deliver nutrition to his stomach.

Crystal became aware of the Clinic for Special Children. Jordan’s grandfather told her, “You are going, and I’m paying for it.” Once there, they met Kevin Strauss, MD, and Crystal finally felt at home.

Within 5 days at the Clinic, Crystal and her family had a diagnosis that Jordan had GM3 synthase deficiency.

With the rarity of Jordan’s case, treatment and management of the disease were unclear. The medications didn’t seem to work and by February the seizures were so bad that Jordan was back in the hospital. This in-and-out of the hospital continued for months. “He barely had strength to breath,” Crystal recalls, “but he could laugh and smile. If you asked him if he was handsome, he’s say ‘uh huh!’” With heartbreaking earnestness, she adds, “He didn’t ask for anything but more love.”

Connor’s fight, Round 1

Jordan eventually succumbed to his rare disease at age 9. Connor’s birth came with much trepidation for his family but thanks to Jordan’s diagnosis, Connor underwent genetic testing at a much younger age. Dr. Strauss made the call to Crystal, informing her that Connor had GM3 synthase deficiency like Jordan.

After the initial shock, pain, tears, and grief, Crystal wanted to know if there were any advancements since her time with Jordan. “I knew if we didn’t do anything what would happen. It’s just a slow agonizing death,” she notes.

Dr. Strauss proposed the idea of meeting with the experts of the Center for Rare Disease Therapy at Children’s Hospital of Pittsburgh of UPMC, who specialize in novel treatments for various rare diseases. He said, “It could possibly be a solution but we don’t know.” Crystal had vowed to fight so the thought of trying anything gave her hope.

She traveled with her husband and three daughters to Children’s Hospital and met with Maria L. Escolar, MD, MS, director of the Program for the Study of Neurodevelopment in Rare Diseases.

Connor’s fight, Round 2

The Center for Rare Disease Therapy at Children’s Hospital explored a few possible options, including a cord blood transplant or a liver transplantation. It was Dr. Escolar who talked to the Mast family about performing an umbilical cord blood transplant as a possible therapy for GM3.

With this new information, Connor’s family had a decision to make. “I knew we had to do something,” Crystal says, “I remember taking my kids home from school and thinking if we don’t do anything, if we don’t do it, we know what will happen. We’re going to do what we feel best, what we think is right, and then we at least know that we tried.” After many days of trepidation and so much prayer, they decided to proceed as long as God kept giving them green lights.

Before proceeding, the Mast family took Connor to the front of their church in Virginia during a service and stood on the altar, surrounded by their church family, and laid hands on Connor and prayed. They prayed for healing, for direction, and that God would be in control of every moment. Crystal believes that their solemn prayers were being answered.

At Children’s Hospital, Paul Szabolcs, MD, chief of the Division of Blood and Marrow Transplantation and Cellular Therapies, prepared Connor and his family for transplant day. Connor received the first doses of chemotherapy to weaken his immune system and avoid rejection of the transplant. Crystal, her husband Dale, and Connor spent their waiting time at the Ronald McDonald House that’s connected to the hospital. Crystal set up her sewing machine in a nook of Connor’s room and passed the time making dresses for her three daughters while they awaited transplant day.

Transplant day was April 4, 2016. Connor experienced a rough recovery from the transplant, including seizures and vomiting. But after some scary nights in the hospital, and after many trials and much tribulation, Connor fully recovered and was ready to return home to family, friends, and their Mennonite community.

Back home

Three-and-a-half months after the transplant, Connor returned home to Virginia. “He didn’t really like his room anymore, he didn’t like his bed,” Crystal says with a laugh, “But he loved being home. He liked having us there.”

By October of 2016, tests showed that Connor was making progress.  According to diagnostic tests, Connor is also building brain tissue and his optic nerves are healthy. Although Connor uses hearing aids, without the cord blood transplant it is likely that he would have completely lost his hearing by age 2.

Crystal believes that, “had we not worked with Jordan and known the outcome, we’d be at the same place with Connor. I will always cherish the time, the love, and the care with Jordan.”