Thankful for Tygh: The Derossett Family
Arriving full-term amidst a flurry of excitement, Tygh Derossett’s birth at a Kentucky hospital in 2016 mimicked that of most newborns. He cried, he received Apgar scoring, and he got a bath. On his second day of life, Tygh’s health care team took a few drops of his blood and sent it to Kentucky’s newborn screening lab.
A few days later, Tygh left the hospital with his parents, Amanda and Aarron, and the new family traveled to their home just south of the state line in Tennessee. Having their first baby was everything Amanda and Aarron imagined, and all was well. When they brought Tygh to his one-week checkup, they assumed everything would be normal. It wasn’t.
“The pediatrician sat us down and said, ‘Tygh has a metabolic disease,’” Amanda says. “We were like, ‘Okay, he’s just going to be skinny.’ Then he followed up with, ‘It’s fatal, and there’s not a cure.’”
Tygh’s newborn screening result was consistent with Krabbe disease. Rare, degenerative, and often incurable, the illness usually claims infants affected by the most severe form of Krabbe disease, like Tygh, within the first two years of life.
Amanda and Tygh Derossett
That appointment set the family on a journey that, unbeknownst to them, had actually started a week earlier when, as part of Tygh’s newborn screening, a test was performed by Mayo Clinic Laboratories for Krabbe disease, as provided through the Kentucky Department of Health’s Newborn Screening Program. Kentucky is one of just nine states that currently includes newborn screening for Krabbe disease, which is estimated to affect about 1 in 100,000 children.
“Had we had him in Tennessee, because they weren’t doing the testing, most likely he would not be here with us, because (Krabbe) wouldn’t have been found,” Amanda says.
For babies with infantile Krabbe disease, early diagnosis is critical to survival, says genetic counselor Amy White, who supports testing in Mayo Clinic’s Biochemical Genetics Laboratory.
“Krabbe disease is so devastating, but at this time we do have bone marrow transplantation, which can really change the natural history of the disease for many patients,” White says.
For a transplant to work, however, the procedure must be performed before symptoms begin, explains Dietrich Matern, M.D., Ph.D., co-director of the Biochemical Genetics Laboratory, who helped develop Mayo Clinic Laboratories’ Krabbe disease screening (Test ID: KD2T).
“Once you show clinical symptoms, there is no use going through that invasive procedure because the loss of function will never be regained, and the disease progresses,” Dr. Matern says. “It’s painful for the patients and everyone caring for them.”
Children affected by Krabbe disease, also known as globoid cell leukodystrophy, do not produce an adequate amount of the enzyme galactosylceramidase, or GALC. GALC maintains the protective myelin sheath that covers nerve cells in the brain and throughout the nervous system. It does so by breaking down types of fat known as galactolipids, galactosylceramide, and galactosylsphingosine (called psychosine). Without GALC, psychosine, which is toxic, accumulates. That triggers a breakdown of the myelin coating. That, in turn, leads to a progressive loss of mental and physical abilities.
Within the first six months of their lives, most infants with early-onset Krabbe disease develop feeding difficulty, extreme irritability, a decline in alertness, loss of head control, and muscle spasms. Eventually, they become unable to swallow and breathe.
The urgency of Tygh’s condition quickly became clear to his parents. Just an hour after the pediatrician visit, where they learned of his diagnosis, the family received a call from a transplant coordinator at Duke University. That same night, they boarded a private jet bound for North Carolina. At the hospital, Tygh was admitted, and, at just 8 days old, started the chemotherapy needed to prepare his body for the stem cell infusion. At 24 days old, Tygh underwent the transplant.
“It was the fastest transplant ever following newborn screening,” Dr. Matern says.
The Derossetts count themselves extremely lucky Tygh was born in a state that screens for Krabbe disease. The addition of Krabbe disease testing to the Kentucky Department of Health’s newborn screening panel in 2015 was the result of grassroots lobbying.
Although other states have been petitioned by similar grassroots movements to add Krabbe disease to their newborn screening panels, those applications are often denied because most single-tier testing methods that measure GALC levels lack specificity and lead to confusing results. Genetic testing also can be unclear because of the presence of variants of unknown significance.
Aarron and Tygh Derossett
“There have been a lot of false positives and a lot of conversations over what to do when you get false positives or genotypes of uncertain significance,” Dr. Matern says. “So there was a lot of confusion and concern that screening causes more harm than good.”
Mayo Clinic Laboratories’ test for Krabbe solves the problem of uncertainty by performing a second-tier test when first-tier results show reduced GALC enzyme activity. The second-tier test uses liquid chromatography-tandem mass spectrometry to measure psychosine levels.
“Our psychosine testing as part of the newborn screening process allows for rapid detection of patients with infantile Krabbe disease, so they can get a bone marrow transplant as early as possible for the best clinical outcomes,” White explains.
When Tygh’s newborn screening indicated low GALC activity, the screening sample was used to immediately measure psychosine and to analyze the GALC gene.
“A common gene variant was negative and instead the genotype was made up of a known mutation and a variant of uncertain significance,” Dr. Matern says. “If this happened in another state and psychosine was not measured, they wouldn’t have paid much attention because it would have been another case of a variant of unknown significance, and follow up would have been delayed. But we had the psychosine, which was very abnormally elevated, so we told our colleagues in Kentucky that this requires immediate follow up.”
Although Tygh’s transplant was difficult, and it didn’t cure him, the therapy has given the family precious time together.
“He looks like he’s 2 years old and is not developmentally where a 5-year-old would be. He doesn’t walk unassisted, and he doesn’t talk, but he’s very smart. He works a tablet and plays shape games and knows all his colors,” Amanda says.
“I think a lot of people think he doesn’t live a normal life because he can’t do this or that. But if you see him, if you’re around him, he’s the happiest kid. He doesn’t know life any differently and loves his life as it is.”
That so many states have yet to add Krabbe disease to their newborn screening means that babies and their families continue to suffer. “I feel that it’s nobody’s right but the parents to decide what their child’s life is worth,” Amanda says. “Tygh’s not what every 5-year-old looks like, but I would still do it all over again.”
Both Amanda and Aarron continue to advocate for expanded Krabbe testing.
“If we hadn’t gotten it done, he would’ve passed away by 2, and what kind of life would that have been? For both parent and child, to watch him be tortured?” Aarron says. “To me, it just seems logical that other states would be able to do the testing. It changed our lives completely.”