New research links a genetic anomaly and some forms of SIDS, or sudden infant death syndrome, which claims the lives of more than 3,000 infants a year.
The research, published in Nature Communications, focuses on mitochondrial tri-functional protein deficiency, a potentially fatal cardiac metabolic disorder caused by a genetic mutation in the gene HADHA.
Newborns with this genetic anomaly can’t metabolize the lipids found in milk, and die suddenly of cardiac arrest when they are a couple months old. Lipids are a category of molecules that include fats, cholesterol, and fatty acids.
“There are multiple causes for sudden infant death syndrome,” says Hannele Ruohola-Baker, professor of biochemistry at the University of Washington School of Medicine, who is also associate director of the Medicine Institute for Stem Cell and Regenerative 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 defect in the enzyme that breaks down fat.”
Unexplained cardiac disease
Lead author Jason Miklas, who earned his PhD at the University of Washington and is now a postdoctoral fellow at Stanford University, says he first came up with the idea while researching heart disease and noticed a small research study that had examined children who couldn’t process fats and who had cardiac disease that was not readily explained.
So he and Ruohola-Baker started looking into why heart cells, grown to mimic infant cells, died in the petri dish where they were growing.
“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,” Miklas says. “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 says. “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.”
In MTP deficiency, the heart cells of affected infants don’t convert fats into nutrients properly, resulting in a build-up of unprocessed fatty material that can disrupt heart functions. More technically, the breakdown occurs when enzymes fail to complete a process known as fatty acid oxidation. It is possible to screen for the genetic markers of MTP deficiency; but effective treatments remain a ways off.
No cure, but hope
Ruohola-Baker says the latest laboratory discovery is a big step towards finding ways to overcome SIDS.
“There is no cure for this,” she says. “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.”
One drug the group is focusing on is Elamipretide, used to stimulate hearts and organs that have oxygen deficiency, but barely considered for helping infant hearts, until now. In addition, prospective parents can undergo screening to see if there is a chance that they could have a child who might carry the mutation.
Ruohola-Baker has a personal interest in the research: one of her friends in Finland, her home country, had a baby who died of SIDS.
“It was absolutely devastating for that couple,” she says. “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.”
The National Institutes of Health, the Academy of Finland, Finnish Foundation for Cardiovascular Research. Wellstone Muscular Dystrophy Cooperative Research Center, Natural Sciences and Engineering Research of Canada, an Alexander Graham Bell Graduate Scholarship, and the National Science Foundation funded the work.
Source: University of Washington