While the rate of sudden unexpected infant death has declined since the 1990s, the Centers for Disease Control and Prevention notes that around 3,500 American babies under one year old die unexpectedly and suddenly every year. Included in those deaths are about 1,700 babies that die from sudden infant death syndrome (SIDS). Seemingly healthy babies die in their sleep from SIDS, and now researchers at the University of Washington have discovered a genetic connection to the problem. This is the first time a potential cause has been identified.
Reporting in Nature Communications, scientists examined a cardiac metabolic disorder that can be fatal called mitochondrial tri-functional protein deficiency (MTP deficiency). A mutation in the gene HADHA causes the disease. Newborns carrying mutations in this gene aren’t able to break down lipids, or fatty molecules, that are found in milk. They experience cardiac arrest when they’re only a couple of months old, and die quickly.
"There are multiple causes for sudden infant death syndrome," said the study leader Hannele Ruohola-Baker, a professor of biochemistry at the University of Washington (UW) School of Medicine. "There are some causes which are environmental. But what we're studying here is really a genetic cause of SIDS. In this particular case, it involves [a] defect in the enzyme that breaks down fat."
A former UW graduate student now a postdoctoral researcher at Stanford, Jason Miklas, was studying heart disease when he first hypothesized that there was a link between children that can’t metabolize fats and sudden infant death. He and Ruohola-Baker started using lab-grown heart cells to investigate further.
"If a child has a mutation, depending on the mutation, the first few months of life can be very scary as the child may die suddenly," he noted. "An autopsy wouldn't necessarily pick up why the child passed, but we think it might be due to the infant's heart stopping to beat."
"We're no longer just trying to treat the symptoms of the disease," Miklas added. "We're trying [to] find ways to treat the root problem. It's very gratifying to see that we can make real progress in the lab toward interventions that could one day make their way to the clinic."
Infants with MTP deficiency have heart cells that can’t break fats down enzymatically to get nutrients out of them - fatty acid oxidation is disrupted. Unprocessed fatty material then accumulates and can interfere with heart function. While there are screening tests for MTP deficiency, there are no treatments. This work may help prevent deaths and create therapeutics, however.
"There is no cure for this," noted Ruohola-Baker. "But there is now hope because we've found a new aspect of this disease that will innovate generations of novel small molecules and designed proteins, which might help these patients in the future."
The researchers are also now looking to a drug called Elamipretide that can aid organs, including the heart, that are oxygen deficient.
Ruohola-Baker has friends who have dealt with SIDS personally, which motivated her to learn more.
"It was absolutely devastating for that couple," she said. "Since then, I've been very interested in the causes for sudden infant death syndrome. It's very exciting to think that our work may contribute to future treatments, and help for the heartbreak for the parents who find their children have these mutations."