Like her two older brothers, who were also born at NYU Langone Health, Emma Hagstrom entered this world uneventfully, on Thursday, October 8, 2020. “She weighed 7.87 pounds, and it was a great delivery,” says Annika Hagstrom, who began breastfeeding her daughter in the newborn nursery. By the time Emma was discharged on Saturday, her weight was down 7 percent.

“The doctors told us that babies can lose up to 10 percent of their body weight after delivery,” recalls Karl Hagstrom, “so they weren’t very concerned.” Throughout the weekend, however, Emma had bouts of diarrhea every time she received either breast milk or formula. By the time Emma’s pediatrician examined her on Tuesday, her weight had dropped 22 percent, and the doctor advised the Hagstroms to head from their home in the Park Slope neighborhood of Brooklyn to the KiDS Emergency Department at NYU Langone’s Ronald O. Perelman Center for Emergency Services.

By bringing Emma back to NYU Langone, the Hagstroms made a fortunate decision. The institution was well equipped to unravel what would prove to be a daunting medical mystery. At Hassenfeld Children’s Hospital at NYU Langone, a multidisciplinary team of clinicians and geneticists marshaled an extraordinary array of resources and expertise to save Emma. The medical detective work that proved critical to cracking the case was provided by NYU Langone’s Pediatric Undiagnosed Diseases Program, a joint venture between the Center for Human Genetics and Genomics and the Department of Pediatrics. The program, one of a small number nationwide that applies the latest genomics technologies to help families and children end their diagnostic odyssey, is supported by the Jacob Goldfield Foundation, the RTW Charitable Foundation, and NYU Grossman School of Medicine.

At Hassenfeld Children’s Hospital at NYU Langone, a multidisciplinary team of clinicians and geneticists marshaled an extraordinary array of resources and expertise to save Emma.

When Emma arrived at the KiDS Emergency Department, she was so severely dehydrated that she had to be transferred to the Pediatric Intensive Care Unit. Critical care specialists faced a very delicate challenge. The excessive sodium in Emma’s blood was drawing fluid from her brain. If fluids were replenished too quickly, the brain could swell rapidly, causing permanent damage.

Once Emma was stabilized, doctors focused on the urgent need to identify the cause of her persistent diarrhea. “If you don’t resolve the problem early enough, there’s a risk of secondary damage to the intestines,” explains Jeremiah Levine, MD, professor of pediatrics and director of the Division of Pediatric Gastroenterology at NYU Grossman School of Medicine.

Emma was switched from a standard formula to one that was soy-based, but it made the problem even worse. At that point, feeding was stopped, and she was nourished intravenously. “I went through the fast with Emma, holding her the entire time,” recalls Annika. “Hearing her cries of hunger was the worst 24 hours of my life.” Without being fed, Emma’s symptoms temporarily improved. “This told us that the diarrhea was probably a reaction to a food substance rather than an underlying disease,” says Dr. Levine. “We just had to figure out which one, and come up with the right feeding regimen.”

Suspecting a congenital cause, Dr. Levine and his team called in geneticist John G. Pappas, MD, associate professor of pediatrics at NYU Grossman School of Medicine. By the time Dr. Pappas joined Emma’s care team on her 11th day of life, the infant’s weight was alarmingly low. “We were losing this baby,” he says, “and we were all sick over Emma’s condition.”

Knowing that Emma’s parents were from Sweden, Dr. Pappas suspected that her illness might be genetic in origin. The country has a higher carrier rate for two genetic mutations that cause a disorder known as glucose-galactose malabsorption, documented in only about 300 cases worldwide. “Glucose is the number one thing we need to absorb,” Dr. Pappas explains, “and it’s present not only in many formulas, but also in breast milk.” Dr. Pappas surmised that Emma’s intestines were unable to absorb glucose, though this deficit would not have affected her in the womb where she was nourished through the umbilical cord, which bypasses the gut.

To confirm his hunch, Dr. Pappas enlisted Gilad D. Evrony, MD, PhD, assistant professor of pediatrics and of neuroscience and physiology at NYU Grossman School of Medicine, who co-directs the Pediatric Undiagnosed Diseases Program with him. Dr. Evrony and his team leverage the most advanced genome-sequencing technologies to pinpoint the root cause for conditions linked to genetic disorders, which account for 70 to 80 percent of undiagnosed diseases. For about half the children born with a rare genetic disease, clinical evaluations alone fail to identify the cause.

“A specific, accurate diagnosis is the foundation of medical care, but I tell parents that we have only a one-in-three chance of finding the genetic cause of their child’s condition,” says Dr. Evrony. “Even when we know which clinical syndrome a child has, often we can’t find the genetic mutation involved.” For an estimated 1,000 presumed genetic diseases, he notes, the causative gene has yet to be discovered. Since its inception in 2019, the program has provided a definitive diagnosis for 16 pediatric patients.

On October 24, Dr. Evrony and his team rushed to perform an accelerated genetic test that used Emma’s blood samples to locate the parts of her genome most likely to have disease-causing mutations. The test, known as rapid genome sequencing, fast-tracks every step of the process, reducing the amount of time needed to obtain a result from several weeks, the usual time frame for standard genetic testing, to less than one week. For critically ill patients like Emma, the expedited test, only recently available at leading hospitals, can be a lifesaver.

While Dr. Evrony’s team was analyzing the genetic data, Emma was placed on a carbohydrate-free formula after nearly three weeks of unsuccessful feeding trials. A form of sugar she could tolerate, fructose, was later added for nutritional balance. To everyone’s relief, Emma’s diarrhea stopped, but only a genetic diagnosis would provide definitive proof of why.

Two days after Emma started the new formula, Dr. Evrony’s team, including Tina Truong, MMSc, genetic counselor, completed its analysis of the DNA-sequencing data and confirmed Dr. Pappas’s suspicion: Emma was officially diagnosed with glucose-galactose malabsorption. The carbohydrate-free formula enabled Emma to thrive, and a carbohydrate-free diet that would become less restrictive as she aged would allow her to live a normal life. “Emma’s story is a shining example of how genetics can make a difference in the lives of our patients,” says Dr. Evrony.

When Dr. Evrony and Truong shared the news with the Hagstroms, “it was tears of joy all over,” says Karl. “We’ve never experienced the amount of empathy and care that was shown to us at NYU Langone. It was astonishing.” Karl and Annika describe Emma, now 2 years old, as extremely energetic and happy, with a feisty personality. “And she absolutely loves food,” says Karl.