“They gave us our daughter back”

By Maureen Gilmer, IU Health senior writer, mgilmer1@iuhealth.org

When Sarah and Tyler Lee look at their baby girl, they are reminded of just how far she’s come and how blessed they are.

The Pittsboro couple, already parents of 8-year-old twins and a toddler, thought everything was routine with this pregnancy until a 30-week ultrasound revealed enlarged ventricles in baby Josie’s brain and the absence of a corpus callosum. The latter is a large bundle of nerve fibers that connect the two brain hemispheres.

They prepared themselves for the possibility of physical and mental limitations in their baby, but before they could learn too much, Sarah went into labor while teaching her Brownsburg West Middle School math students.

Josie Lee entered the world fast – within 2½ hours – and early – at 34 weeks. Doctors at the northside Indianapolis hospital where she was born March 3 of this year soon reached out to the molecular genetics team at Riley Children’s Health.

They were concerned that the baby’s lactate levels were fluctuating wildly and consulted Dr. Brett Graham, who specializes in medical genetics for Riley’s Medical & Molecular Genetics team.

That started a chain of events that Sarah Lee believes saved Josie’s life.

Testing revealed what Dr. Graham had suspected, even though he hadn’t yet laid eyes on the child.

Josie has a rare metabolic condition called pyruvate dehydrogenase complex deficiency, which disrupts how the body processes glucose. Instead of turning glucose into energy to power the body, it turns it into lactic acid, which can build up and attack the brain and other organs.

Doctors also discovered Josie had suffered subclinical seizures due to the buildup of lactic acid and brain damage in utero from her condition.

“We were thinking this was not a life-sustaining condition,” Sarah said, adding that she and her husband were even discussing final arrangements for their child.

But they also knew that they wanted Josie to have a fighting chance.

After all, Sarah reasoned, perhaps Josie came early because she knew she needed help.

“We have to go where the experts are,” Sarah said she and her husband decided. “There’s only one (board-certified) metabolic team in the state, and they’re at Riley.”

Even before tests confirmed what Dr. Graham suspected, he advised the team at the other hospital to start her on a ketogenic diet to manage her levels of lactic acid and control her seizures.

The difference was almost immediate.

“As soon as she was put on that diet, her lactates fell to a normal range for the first time,” Sarah said.

Her daughter suffered some brain damage in utero, “but if we had not gotten in touch with Dr. Graham and gotten her on the ketogenic diet, it would have continued.”

Dr. Graham remembers consulting with the Lees about the results of the genetic testing, first on the phone before they came to Riley.

“It’s important to give hope where hope is due but also be clear about the range of possibilities,” he said, noting that the condition Josie had can be terminal in the first weeks of life.

“But Josie responded very well to the ketogenic diet, which we’re all grateful for,” the physician said.

When the Lees arrived at Riley, they were met by medical geneticist Dr. Molly McPheron.

Sarah recalls hearing words like “manageable condition” and “ketogenic recipes.” Even talk of “favorite snacks” like pork rinds for kiddos.

“I just remember thinking, pork rinds? You need teeth to eat those. Are you suggesting we may have enough time with our daughter that she will have teeth and eating food?”

That was when everything changed, Sarah said, through tears.

“There was hope in the air. There was experience with this condition, and there was a plan.”

The Riley NICU was the couple’s home from late March to late May, during which time the Lees recall so many nurses and doctors advocating for Josie and for the family.

“Nurse practitioner Kathy Green … has been the glue that has held this team together from Josie’s very first day at Riley,” Sarah said. “She has been fighting for Josie every day.”

In addition, she said, “the genetics and metabolism people changed everything. They had a plan, they had experience. … They gave us our daughter back.”

During that time, neurology ketogenic dietitian Taylor Parrish and the metabolic team came up with a recipe to keep Josie’s lactates in the normal range and prevent further seizures.

The specialized ketogenic formula uses small amounts of Sarah’s breast milk mixed with the right amounts of fat, protein and supplements to nourish Josie without taxing her body’s ability to convert carbs.

“Because she can’t break down carbohydrates in breast milk, she kept getting higher lactic acid buildup,” Parrish explained. “That’s what was damaging her organs and her brain. We needed to come up with another way for her to get nutrition so her cells can still get energy.”

The ketogenic diet is high in fat, adequate in protein and low in carbohydrates, so now Josie’s body is using ketones for fuel, Parrish said.

“Her brain cells are able to use these ketones as energy instead of glucose. Because we were able to get her on the ketogenic diet when we did, we were able to prevent further damage.”

Josie is closely monitored to ensure she is receiving the appropriate amount of nutrients, but she is doing well, Parrish said.

“She is growing well, and she has been stable, which is great. Josie’s parents are huge advocates for her.”

While the ketogenic diet has been successful in treating Josie’s condition, it’s just the beginning, Dr. Graham said.

“The development of therapeutics for rare diseases is exploding. This is a dietary treatment to bypass the defect, but there are ongoing clinical trials for more direct treatments,” he said. “Even with rare diseases, the future over the next several years is a rapidly changing landscape.”

Genetic testing early in critically ill neonates is also making a difference in their care, Dr. Graham said. Dr. Kristen Suhrie, director of perinatal genetics and an attending neonatologist at Riley, is spearheading the effort.

Previously, genetic testing would take several weeks or months to come back, but by partnering with Riley’s neonatology team to more quickly identify babies who meet the criteria for testing, they are able to submit and get results back from a diagnostic laboratory in one to two weeks.

That’s valuable time during which treatment can begin.

“We’re getting timely results in patients we suspect could have an underlying genetic disorder,” Dr. Graham said. “And in a level 4 NICU, that’s a pretty significant fraction of the patients.”

Josie, who has a G-tube delivering her ketogenic formula, continues to grow and change, her mom said.

“She is gaining weight and growing like a weed. We are incredibly blessed to be where we are right now,” Sarah said, adding that the family is “taking one day at a time with our sweet girl, knowing she has a purpose and God has a plan for her life.”

“In our eyes, this is a place of miracles,” she said about Riley. “It has completely changed the trajectory of our daughter’s life. We don’t know what tomorrow holds, for any of us really, but we know that we have gained more time with our daughter than we had originally thought.”

And for that, they are eternally grateful.