In 2014, National Geographic debuted its 125th anniversary issue. On the cover was a grid of 25 different faces, including men, women and children, titled “The Changing Faces of America,” which depicted what the average American could look like in the year 2050 as racial mixing increases with each new generation.1 The accompanying article talks about the increase of Americans who identified as more than one race–from 9 million on the 2010 U.S. Census, compared to 6.8 million on the 2000 census.
Although the United States has long been known as the great melting pot of the world, this ethnic diversity presents a big challenge in the medical community, specifically in diagnosing cystic fibrosis.
Using the Cystic Fibrosis (CF) Foundation Registry, Stanford University researchers looked at CFTR genotyping across different racial and ethnic groups. The study published in The Journal of Molecular Diagnostics found differences in the genetic coding of whites and nonwhites, whom are often diagnosed at a later age. Researchers believe one reason for this ethnic disparity in the diagnoses of cystic fibrosis is that the variants examined in the most common cystic fibrosis newborn screening panels do not include all of the possible mutations present in nonwhite populations.
“If you order the very basic cystic fibrosis mutation screen, it only covers the most common mutations,” explained Whitney Brown, MD, director of the Cystic Fibrosis Program at Inova Advanced Lung Disease and Transplant Program based in Falls Church, Va. Two years ago Brown diagnosed a 21-year-old African American man with cystic fibrosis after supplementing a basic cystic fibrosis screen with a sweat chloride test. “When I ordered this test for him, only one of his mutations was in that common 32. So, if I hadn’t done the sweat chloride test and didn’t have all of the history, that would suggest he was a carrier and didn’t have the disease.”
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The young man had been told by other providers that he had asthma, but cystic fibrosis, an inherited disorder that damages the lungs and digestive system, can be far more life-threatening.
And he is not alone–with the researchers at Stanford finding 30% of Hispanics, 38% of blacks and 41% of Asians in the registry did not even have one copy of a cystic fibrosis mutation that was common in more than 80% of whites and Native Americans. In total, there are more than 1,800 known mutations of the cystic fibrosis gene according to Cystic Fibrosis Foundation.
Cystic fibrosis screenings are now universal across the U.S. Each state’s health department makes a point of disclaiming on their websites the fact that there is still a chance a baby has cystic fibrosis even if their basic screen comes back negative. As a result, follow-up testing may be ordered.
“We should not exclude the diagnosis of cystic fibrosis without sequencing the gene for anyone we’re suspicious of,” stressed Brown. “We shouldn’t stop at the 32 or the 100th and say, ‘Well, we can’t find a mutation so they probably don’t have CF,’ and look harder.”
An early diagnosis is important, as with any illness or disease, because it allows treatment to begin sooner before people start showing symptoms. Studies find that children with cystic fibrosis who receive immediate care have improved growth and lung function, reduced hospital stays and a better life expectancy overall.
Some treatments similarly depend on identifying the exact mutation, meaning challenges can remain even after a cystic fibrosis diagnosis has been confirmed. As the world of healthcare moves toward personalized medicine, pharmacogenetic therapies are being developed to target specific genetic mutations.
Kalydeco, for example, made by Vertex Pharmaceuticals of Cambridge, Mass., targets the G551D mutation in patients 6 years and older. While researchers saw positive results in the 2012 clinical trials, the drug is expected to help only a small fraction of cystic fibrosis patients–specifically 4% of people living with cystic fibrosis who have the G551D mutation.