Girl’s rare disease takes family ‘through trials and tribulations’
In three hours, Paul Shelsta would take the field for his first football game as offensive coordinator for the Hartford Union High School Orioles. That night in August 2016 was to be a big moment for the physical education teacher. He planned to arrive at the game early.
But as he got ready to leave the family home in Richfield, Shelsta glanced at his usually cheerful 10-year-old daughter, Alaina, and he knew something was off.
Her blue-green eyes had a faraway look that had always meant trouble. Since age 2, she had suffered seizures, sometimes dozens in a single day caused by an extremely rare genetic disorder. That distant stare was the telltale sign that she was in the midst of a seizure.
The blond girl known for her hammerlock hugs kept asking about her younger sister, Alexis.
Alexis wasn’t home, Shelsta responded, but Alaina insisted: “She’s right there.”
“What’s wrong?” the father asked. Then he watched Alaina bury her head in her hands.
“My world is just not right,” she said. For most of her life, Alaina’s world has been an extremely rare medical prison called GLUT1 deficiency syndrome or De Vivo disease, after Darryl De Vivo, the neurologist who identified it in 1991.
In Alaina, the vital delivery of glucose to the brain is disrupted because of a mutation that was not inherited from her mother or her father but occurred spontaneously in the embryo. Glucose, which helps power the organs and nervous system, is also the brain’s most important source of energy, allowing us to think, speak and control movement throughout the body.
Only 500 cases of GLUT1 deficiency have been described in medical literature, though some research suggests that it may occur more often and go undiagnosed.
Even in the very small universe of GLUT1 patients, Alaina stands out. Ninety-nine percent of patients with the disease can be treated with a ketogenic diet — low in carbohydrates, high in fats. Alaina is among the 1% who cannot tolerate the diet.
After 12 years and seemingly endless changes in treatment, she has become only the sixth patient in the world to be treated for the condition with a drug called diazoxide. The medication is used to treat hyperinsulinism, a severe condition marked by low blood sugar levels that can lead to seizures and brain damage.
The use of diazoxide is part of a complex and delicate dietary-pharmaceutical balancing act. Too little of the medication, and she is afflicted with seizures. Too much, and her blood sugar rises toward the diabetic range. The drug also causes side effects, such as swelling in the feet, ankles and face, all of which Alaina has experienced.
Preserving the proper balance of food and medicine is a 24-hour a day endeavor. Alaina wears a device on her abdomen that constantly monitors her bloodglucose levels and sends updates to her cellphone every five minutes.
Her parents, both physical education teachers in the local schools, have grown accustomed to the frequent shifts in Alaina’s diets and drug regimens. They know to watch for changes in her behavior and mood and to respond quickly whenever she says, “I don’t feel well” or “My stomach hurts.”
There are weeks when Chris is on the phone to Alaina’s doctors every day, even several times a day. Doctors, especially Alaina’s primary physician Patricia Liethen, have grown accustomed to frequent calls from the Shelstas, some late at night.
Paul, who works at Richfield Middle School, teaches a health class at the same time Alaina has recess. His classroom has a window that looks out on the recess area, and several times during class his eyes scan the schoolyard for his daughter.
Chris maintains a daily spreadsheet detailing everything Alaina eats, every medication she takes, every drop and every spike in her blood-glucose level.
The entry for a recent morning begins:
“(Alaina) woke up around 8:30 a.m. complaining of being real light-headed — didn’t want to eat or take any medicine before leaving for her blood draw; we had her drink some more water and a little chocolate milk; by the time Paul got her to the hospital for the blood draw, Alaina was feeling even worse... Paul told me he can’t take her in (to the hospital), they were going to get some food... after they received the food Alaina had to have Paul pull over in the parking lot because she thought she was going to get sick — she actually ran to a garbage can but didn’t (get sick).”
“They’ve been through trials and tribulations. They’ve had short periods of calm,” said the Rev. James Hill at United Church of Christ in Jackson where the Shelstas attend services. “It has been a volatile path that Alaina’s health has been on.”
“A recurring theme is that her medication will work for a little bit, sometimes up to three months, and then her body adjusts” and the treatment becomes ineffective, Paul Shelsta said.
“We always say that she has every right to be mad at the world and she’s not. She’s always smiling.”
On a ‘diagnostic odyssey’
Alaina was born in April 2006, but it was almost two years before her condition began to reveal itself.
Another seven years would pass before doctors diagnosed it. The long gap between the start of symptoms and the diagnosis is typical.
On average, the first symptoms of GLUT1 appear at seven months of age, but children are not diagnosed until they’re 7 years old, said De Vivo, who discovered the condition while working as a neurologist at Columbia University Irving Medical Center in New York.
“So many people have told me: ‘I have been on this diagnostic odyssey until you finally told me what was wrong.’ ”
The Shelsta family’s odyssey began one day in late March 2008, when Paul looked over at Alaina in her high chair. Suddenly her face turned red and she appeared to be having trouble breathing. He thought she was choking.
Paul immediately removed his daughter from the high chair and flipped her so that her stomach rested on his forearm. He began striking her back to dislodge the food. Alaina’s breathing began to calm and she appeared much better. The strange thing was no object had flown out of her mouth.
It was only after a second incident weeks later that the Shelstas began to think Alaina might have had a seizure, not a bout of choking. In the second incident, her whole body locked up. Alaina fell over, her lips turned blue and her eyes rolled back.
She was taken to Aurora Medical Center in Washington County, then to Children’s Hospital of Wisconsin. Alaina had a second seizure in front of the paramedics as they were preparing to take her to Children’s Hospital. When she was on the stretcher waiting, Paul remembers her tiny hand grabbing his finger.
“I couldn’t believe how strong her grip was,” he said.
During that first visit to Children’s Hospital, doctors took an MRI scan and gave the family anti-seizure medication.
Those first few seizures were what doctors call grand mal seizures. They are characterized by a 10- to 20-second loss of consciousness, then muscle convulsions.
The thousands of seizures she has had since then are very different. Alaina does not lose consciousness. Her body does not convulse.
The Shelstas said that often during these seizures, Alaina goes into a sleepyeyed stare as if she is looking, not at people, but through them. Sometimes her eyelids flutter. Her lips smack. She has difficulty keeping her balance.
These are called absence seizures. Although they come with none of the violent convulsions of the grand mals, they register as sharp peaks on scans that measure electrical activity in the brain.
Between 2008 and 2015, Alaina made numerous visits to Children’s Hospital, yet her condition remained a mystery.
Then, in January 2014, she began having episodes in which her legs would suddenly go wobbly.
Chris Shelsta said her daughter’s legs “looked like noodles and she wouldn’t be able to walk for a time.” Some episodes lasted a few minutes, others went on for hours.
At first, doctors thought she had ataxia, a balance problem brought on by damage to the brain, nerves or muscles.
Finally, in October 2015, after undergoing two spinal taps to measure her cerebrospinal fluid, Alaina was diagnosed with GLUT1 deficiency.
Discovering a new disease
In 1991, when neurologist Darryl C. De Vivo was in his 13th year on the faculty at Columbia University, he was asked to examine a 7-month-old boy. The baby had been experiencing seizures since his third month of life.
The infant puzzled De Vivo.
The child’s brain scans appeared normal. He did not have hypoglycemia, low blood-sugar levels in the body.
Yet a spinal tap showed unusually low levels of the sugar glucose in his cerebrospinal fluid, the liquid that surrounds and cushions the brain.
“I couldn’t figure it out,” De Vivo said in an interview with the Milwaukee Journal Sentinel.
Why should there be a healthy level of glucose in the body, but not in the brain?
De Vivo determined it had to be a defect in the protein that carries glucose through the blood-brain barrier.
The barrier is formed by tightly linked endothelial cells, which line the blood vessels. The protein that carries glucose past the barrier is called the GLUT1 transporter.
In September 1991, De Vivo and colleagues published a paper in The New England Journal of Medicine discussing the male infant and a 2-year-old girl with the same condition.
While discovering a new disease and determining its cause is a career event for a doctor, De Vivo went a step further.
The 1991 paper also named a treatment that had proved successful in the first two patients. Both were placed on a ketogenic diet, which delivers fuel to the brain without requiring the help of the GLUT1 transporter. The diet remains the standard of care today for most GLUT1 patients.
Over the years, however, De Vivo found that “a few patients don’t tolerate the ketogenic diet for reasons we don’t fully understand.”
He tried the medication diazoxide on five such patients. Although the patients improved at first, they later grew worse than they’d been before receiving the drug.
Unless it was carefully managed, the medication pushed their glucose level too high, and at the same time reduced the number of GLUT1 transporters. That left the patients essentially back where they started: not enough glucose in the brain, resulting in seizures.
“So I put it away,” De Vivo said of diazoxide.
Dietary precision
After her diagnosis in late 2015, Alaina started on the ketogenic diet and began a new relationship with food. Each portion had to be measured with precision.
“A meal would have 42.5 grams of bacon and it had to be exact,” Paul Shelsta recalled. “Then 13 grams of strawberries. Then, always cream and (melted) butter. We had them in separate containers.”
“I was fine with the cream,” Alaina said, “but I didn’t like drinking the butter.”
Paul Shelsta would make two dinners each night: the one for Alaina, and a completely different one for the rest of the family. Sometimes, preparing dinner took him three hours.
At school, Alaina could not eat the chocolates, cookies and candies that students and teachers brought in as treats. She would accept the treat, then bring it home to exchange for something in the “prize box” that the Shelstas kept. The box contained stickers, small toys and plastic figures called Shopkins.
By December 2015, two months after starting the diet, Alaina grew very sick. Her cholesterol level shot well past 300 (200 is considered high for a child of 10); her triglycerides surpassed 400 (200 to 499 is considered high).
Doctors revised her diet between January and March 2016, but her seizures worsened. She often looked flat and emotionless, on the verge of falling asleep. She had stomach pains and sunken eyes ringed by dark circles.
Although Alaina enjoyed her school in Richfield, teachers noticed that she was so tired she had to take naps during class.
In April, doctors changed the ratios of different foods in her ketogenic diet. She had to consume much more butter and heavy whipping cream.
She spent her 10th birthday in the hospital.
Then her doctor at Children’s Hospital tried taking her off the special diet.
“She was a completely different kid, smiling, laughing,” Chris said. “She could have anything she wanted.”
She ordered pizza. When she had her first drink or orange juice she screamed: “Dad! It tastes so good.”
The summer of 2016 was magical. She ate what she pleased and suffered no seizures.
Then came August. The football game, Paul Shelsta’s debut as offensive coordinator. Alaina’s distant stare.
“He gave me a call and said, ‘Alaina’s not good,’ “Chris recalled. She came home to watch her daughter while Paul coached and tried to concentrate on the game.
Sometimes the disease fights back
In 2017, the Shelstas took Alaina to New York to see De Vivo, who joined the team caring for Alaina. The family had grown frustrated with diets and medications that teased them with a few good weeks or months but failed in the long erm.
“It is true that the body can adapt to any and all anti-seizure medications that I use,” explained David Hsu, a neurologist at American Family Children’s Hospital in Madison, who began caring for Alaina in 2019 after her doctor in Wauwatosa retired.
“There is a significant minority of people with epilepsy for whom each new medication either quickly or later becomes ineffective,” Hsu said, explaining that Alaina’s seizures are epileptic.
“Epilepsy is a living thing that we fight. Sometimes it fights back at many different levels.”
Recognizing that there would be more trips to New York, Chris resigned as head girls basketball coach at Hartford Union High School. She loved her 11 years coaching the team, but said, “I knew I would not be able to give the attention to it that was needed.”
The Shelstas faced a similar dilemma at home, where so much time was devoted to Alaina’s condition that her younger sister, Alexis, sometimes felt overlooked.
Paul and Chris decided they would bring Alexis with them when they took Alaina to New York for visits with De Vivo. They would make sure, too, that they did not spend all of their time in the doctor’s office, but planned at least one activity that was purely fun: visiting Central Park or taking the Staten Island Ferry.
“We didn’t want to lose Alexis in all of this,” Chris said.
Measurements every five minutes
In the years since De Vivo “put away” diazoxide there had been a significant advance. Researchers had developed a device that attached to a patient’s abdomen and could send blood-glucose measurements to a cellphone every five minutes.
The advent of the new device encouraged De Vivo to revisit diazoxide with Alaina, whose illness had resisted every diet and medication doctors had tried.
In April, she began taking the medication and wearing the glucose monitoring device.
During the course of her disease, she has been asked to rate how she feels each day on a scale of 1 to 10 with 10 being best. Alaina tended to give high ratings, but only 9s or 10s meant that she was actually well.
“We feel that we’re on the right track,” Paul Shelsta said.
Ellen Connor, a pediatric endocrinologist on Alaina’s care team at American Family Children’s Hospital, said the medication is “improving her life,” though she stressed that the doctors are constantly asking themselves: “Are we making improvements significant enough to be worth the side effects?”
A balancing act that never ends
Diazoxide has helped Alaina, though it is no magic pill.
For parents and doctors, managing her health is a complex and unrelenting labor of love.
Because diazoxide causes her to retain excess fluids, she takes a diuretic called hydrochlorothiazide to get rid of them.
But hydrochlorothiazide causes her to lose potassium. The body needs potassium to keep the heart beating regularly, and to help nerves function and muscles contract. So, Alaina takes potassium pills to compensate for the diuretic.
Maintaining this delicate balance forces doctors to change her regimen on a weekly, even daily basis, and to a degree many parents would find staggering.
On July 13, for example, the Shelstas had a teleconference with two of Alaina’s doctors.
At the time, she was taking diazoxide three times a day: 8 a.m., 4 p.m. and midnight. Based on her most recent blood sugar levels, the doctors had just decided to raise the morning and midnight doses by 10 milligrams.
Also, she was taking five potassium pills in the morning, another five at night.
Also, she was taking two tablespoons of corn starch in the morning, two more at noon and three in the evening. Corn starch helps keep her blood sugar levels up.
Also, she was taking a cap full of Miralax with four to five ounces of lemonade twice a day to prevent constipation and ease her stomach pains.
Also, she was taking the hydrochlorothiazide to help her body get rid of excess salt and water.
This was the treatment plan at 9 a.m. July 13, a Monday.
A few hours later, Alaina’s latest blood results came back and Connor said the potassium levels were dropping, likely as a result of the hydrochlorothiazide. So doctors stopped that drug and replaced it with another called amiloride.
Over the next two weeks, Alaina’s seizures began increasing and her blood sugar level dropped into the 80s, well below the 140 to 160 that doctors believe to be Alaina’s “sweet spot.”
Connor recommended the family add more diazoxide and return hydrochlorothiazide to the lineup.
The next tests showed Alaina’s blood sugar level was still too low. Connor consulted a kidney specialist, Hsu, and Santhi Logel, a pediatrician training in endocrinology.
Then Connor told the family that Alaina should discontinue amiloride, which was not preventing swelling, and replace it with a new diuretic called spironolactone. She would take one pill twice a day.
The new regimen began on a Sunday.
Monday night Alaina felt light-headed. Tuesday she was worse.
Alaina was now suffering dehydration thanks to the diuretic pills, “so we started pumping her with Gatorade,” Chris said, “which was enough to get her to take the diazoxide and eat a little something.”
On Thursday, doctors were to examine results from Alaina’s most recent blood draw.
“Things could definitely change again tomorrow,” Chris said.
They did.
On Friday morning, the Shelstas discovered Alaina had gained more than three pounds in 12 hours. She was retaining too much water. Her blood sugars were still too low and she continued to have seizures. Doctors changed dosages of all of her medications.
“You feel like you are constantly chasing numbers,” Chris said. “You feel like you are trying to do everything to keep the (blood sugar) numbers up, but then she still drops. You feel helpless at times.”
Happy, popular and a hugger
Despite all she has been through, Alaina is often happy. She is popular at school and has many friends in the neighborhood.
To celebrate her 14th birthday on April 19, neighbors held a parade of roughly 100 cars. They honked their horns and cheered.
Such are birthday parties in the age of COVID-19.
Before COVID, Alaina would high-five her way down the halls of Richfield Middle School. These days she enjoys watching movies with friends via Face Time. “Aladdin” is her favorite.
She and her sister play basketball outside and have their share of sibling arguments, especially when Alexis tries telling Alaina how to dribble or shoot. But Alexis also watches out for her big sister.
“She is our second set of eyes for Alaina,” Chris said. “She has come to us numerous times to let us know when Alaina’s having episodes.”
Among family and friends, Alaina is known as a big hugger. She is eager for the day when it will be safe to hug again.
“An Alaina hug is like the tightest hug you can imagine,” says Hill, her pastor at United Church of Christ. “It just fills your whole body with warmth. If she hugged a tree, she’d strangle it.”