In genetic diseases for which treatments exist, rapid diagnosis is critical for neonatal interventions that lessen morbidity and mortality. Sarah Maxey Photography
Pompe disease is a rare genetic disorder that often affects babies at birth, disabling the heart and skeletal muscles and causing seizures. Without medical treatment, most infants die of heart failure by their first birthday. Enzyme replacement therapy, if started early, can add years to a child’s life.
But here’s the problem: It takes several weeks to diagnose genetic diseases in newborns, and in some cases, that’s simply too long.
“Even to look at a single gene has not been possible in a time frame that makes sense for a baby with a life-threatening illness,” said Dr. Stephen Kingsmore, director of the Center for Pediatric Genomic Medicine at Children’s Mercy Hospitals in Kansas City and a study author. “And pretty often, results come back after a baby has died.
There are more than 7,500 genetic diseases — that is, diseases caused by a mutation in a single gene. They affect 3 to 4 percent of children in the U.S. and account for more than 20 percent of infant deaths. Genes have been identified for 3,500 of those disorders. Pinpointing the disorder can enable quick treatment when treatment is available, and limit unnecessary testing when it’s not.
“We know if we can get treatment immediately to the baby, we minimize the disease’s severity,” Kingsmore said.
Kingsmore and his team have developed new software designed to cut this critical diagnosis time to two days, down from four to six weeks. The results were published on Wednesday in the journal Science Translational Medicine.
The new software would allow doctors to punch symptoms into a program. The program then matches those symptoms with corresponding gene variants, providing a narrowed-down list of gene candidates. Geneticists can use that list to help pinpoint the disease.
In six of the seven newborns they screened, they were able to successfully diagnose the illness. And in one case of a baby with neonatal epilepsy, they found the disease-causing mutation in about two minutes, said Dr. Carol Saunders, a clinical laboratory director at Children’s Mercy Hospital and a study author.
There are limitations to the technology though. In a different case, in which a newborn had cardiomyopathy, congenital cataracts and high lactic acid in the blood (all symptoms commonly associated with mitochondrial disorder), doctors failed to pinpoint a disease-causing gene.
“We couldn’t find a smoking gun,” Saunders said. “There are some types of mutations that are obvious when you see them. There are others that you might overlook — that are not as devastating to the gene.”
Narrowing the list of gene variants will in some cases, allow doctors to speed treatment, which can be critical in the newborn period, said Dr. David Bick, chief of the medical genetics division in the department of pediatrics at the medical college of Wisconsin and not involved in this study. He pointed to a case of Pompe disease at his hospital.
“We had a case a few years ago where we diagnosed the child within a day or two of birth with Pompe, and we were able to institute an enzyme replacement therapy,” Bick said. “That child is now doing extremely well.”
When the patient’s symptoms fit a gene variant that’s well understood, this technology can be extremely useful, he said. But for the many genes that are less understood, geneticists will still face a more laborious search.
“It will do a good job for a few thousand genes, and it will do a good job in a percentage of children,” Bick said. “But it’s still important to go deeper when it fails to yield an answer.”
Margaret Warner will interview Stephen Kingsmore on Wednesday’s NewsHour broadcast.
Photo credit: In genetic diseases for which treatments exist, rapid diagnosis can be critical to lifesaving intervention. Photo by 2012 Sarah Maxey Photography.