This post originally appeared here.
Imagine having a newborn baby who isn’t doing well. Instead of moving her hands and legs spontaneously, she’s limp, like a rag doll in your arms. She has trouble breathing on her own and feeding.
Imagine a 6-year-old who until recently was doing well in first grade. But now he has seizures, can’t walk, has difficulty thinking clearly and is falling behind other kids in his class.
Now, imagine being a parent of one of these children and taking them from doctor to doctor trying, without success, to find out what is wrong. There probably aren’t enough synonyms in a thesaurus to describe how you’d feel.
In an effort to put an end to these diagnostic quests for children with chronic genetic disorders and their families in the Mountain West, the Mark and Kathie Miller Pediatric Genomics Fund will contribute $3.6 million over the next five years to support a pair of pediatric genetic research programs at the Center for Genomic Medicine (CGM) at University of Utah Health.
The gift will allow the Utah NeoSeq Project and Penelope Program to expand and refine their testing and diagnostic efforts. NeoSeq uses rapid whole genomic sequencing (rWGS), cutting-edge computational analysis, and medical and scientific expertise to diagnose genetic disease quickly in severely ill newborns. The Penelope Program applies those same innovative approaches to children with undiagnosed and rare diseases,
“We are excited to be a part of this extraordinary program,” Mark and Kathie Miller say. “We are confident it will become a resource and a model for the entire country.”
Individuals who would like to join the Millers in supporting the NeoSeq and/or Penelope Programs can reach out to Steven Finkelstein here.
Transforming Neonatal Care and Diagnosis
About one in four newborns treated in neonatal intensive care units (NICU) are suspected of having some sort of genetic disorder, says Sabrina Malone Jenkins, a neonatologist at U of U Health, and the principal investigator of NeoSeq.
A handful of NICUs in the U.S., including at U of U Health, are now searching for genetic causes of disease in these infants by reading, or sequencing, the three billion DNA letters that make up the human genome.
In the past, it could take weeks, months or even years of computational and manual analysis to diagnose an illness. Often, the causes weren't determined. Neonatal physicians say the crucial time gap needs to be slashed so they can begin providing the appropriate care as soon as possible.
To address this deficit, CGM investigators collaborated with ARUP Laboratories to established the Utah NeoSeq Project in 2020. In some cases, this program can provide a genetic diagnosis to NICU patients in less than a week. Since it began, NeoSeq has diagnosed about 35% of its patients, based on genetic analysis of blood samples from 55 infants and their parents.
“This is life-changing research for our patients and their families,” Malone Jenkins says. “It allows the care team to identify what is wrong with the baby and personalize any treatment that can be offered. It also offers some clarity to a family that helps them understand why their baby is so sick and why they’re in the NICU. It gives families and caregivers a roadmap of potentially what to expect moving forward.”
Malone Jenkins believes support from the Miller Fund will allow NeoSeq to test more NICU infants and let researchers conduct more extensive genomic sequencing, which will lead to better detection of rare genetic disorders.
“We’re very excited and grateful for the generosity and support of the Miller family,” Malone Jenkins says.
Solving the Most Complex Pediatric Cases
The Penelope Program benefits children with serious, complex conditions who remain without a diagnosis despite multiple evaluations.
A multidisciplinary team of clinicians and researchers from the University of Utah thoroughly examines and assesses the children, searching for clinical clues and changes in their DNA that can reveal a diagnosis. Their efforts also capitalize on the expertise of key partners from ARUP Laboratories and the Utah Center for Genetic Discovery, renowned for developing innovative genomic analysis tools.
Since its founding in 2016, the Penelope Program has evaluated 119 families and identified several genes associated with rare conditions including neurological diseases and bone disorders. Nearly 50% of Penelope patients have received a diagnosis.
“After all they’ve gone through, families usually come in expecting that we’re going to tell them that we didn’t find anything,” says Lorenzo Botto, the principal investigator for the Penelope Program and professor of pediatrics at U of U Health. “When we do find a diagnosis, this takes a big weight off their chests. But when we don’t find a diagnosis, we do not give up—we stick with families because there is hope.”
With a firm diagnosis, clinicians can improve their care while avoiding redundant tests or exams; families can connect with other families with the same condition and find a “home” and researchers can work on finding better treatments.
Importantly, by combining the team expertise with advanced genomics, the typical diagnostic odyssey that can last for years can be dramatically shortened, Botto says.
The Miller gift will allow the Penelope Program to evaluate an additional 75 patients and their families over the next five years.
“This support is a wonderful gift to families and science,” Botto says. “It will help grow the program so that it becomes part of the broader pipeline that goes from diagnosis to searching for new treatments.”
The Penelope Program is one of a dozen clinical sites in the National Institutes of Health-supported Undiagnosed Diseases Network (UDN). The UDN is a national consortium of medical and research centers working together to improve diagnosis and care of patients with undiagnosed diseases.
Families can apply to participate in the Penelope Program through their health care providers to University of Utah Health Pediatrics.