Searching for Answers: Celiac and Gluten Sensitivities
Counting the Cost
[Updated May 20, 2015]
When teachers noticed 10-year-old Abby was spending more time in the bathroom than at her desk, they knew she wasn’t just trying to skip class. Abby had always loved learning and was highly motivated. Plus, it wasn’t just school she was missing.
“Abby loves sports but she was ducking out of soccer, lacrosse and basketball games because of stomach cramps,” recalls Abby’s mom, Donna Williamson* of Baltimore, Maryland. “If she made it through a game, she rushed to the port-a-potty afterward.” Abby’s increasingly frequent bouts of diarrhea were embarrassing and her painful stomach cramps and bloating interfered with her active lifestyle.
With food allergies in the family, Williamson suspected that something Abby was eating was to blame. She took her daughter to the family doctor who tested her for more than 60 potential food allergens.
“The only thing that came back positive was gluten," Williamson says. "It was off the charts."
Abby immediately immersed herself in the gluten-free diet. “She learned the diet backward and forward,” her mother says. But months later, when strict adherence to the diet hadn’t totally eliminated Abby’s uncomfortable symptoms, Williamson took the girl to a series of specialists, including two pediatric gastroenterologists.
Examining Abby closely and going through her medical history, the doctors considered various illnesses but ultimately focused on acid reflux and celiac disease. An endoscopy showed mild reflux but no evidence of celiac, possibly because Abby had been eating gluten free for months, including during the period when the procedure was conducted. She was prescribed reflux medication.
“Abby dutifully took the medicine but she didn’t think it was helping,” Williamson says. “Eventually she asked me if she could stop both the medication and the gluten-free diet to see if things might clear up all on their own.”
But things didn’t improve. In fact, Abby’s symptoms worsened. She was having an even harder time making it through sports practices and games without bathroom episodes and it was becoming even more challenging to focus at school.
“Abby became depressed and didn’t seem like herself. She wasn’t enjoying herself and never seemed to be smiling any more. She was typically such a bubbly girl and it really upset us to see her suffering and withdrawing,” says Williamson.
Although Abby was scared to undergo more medical tests, she felt so sick that she agreed to a second round of testing for celiac disease, including a repeat endoscopy.
“This time, the blood tests for celiac were positive so we expected the endoscopy to confirm that she had the disease,” Williamson says. But surprisingly, the second endoscopy showed no signs of celiac. Results were completely normal.
“The doctors called her a ‘diagnostic dilemma,’” Williamson recalls. “From her symptoms and blood tests, there was every reason to suspect she had celiac disease—but the biopsy didn’t confirm it. The doctors had told us the biopsy is the gold standard for celiac diagnosis. We were so frustrated. We didn’t know where to go from there.”
As Abby’s physicians discussed performing other more invasive tests, they also mentioned there was a genetic test for celiac disease. “They explained it was a different approach,” says Williamson. “It couldn’t diagnose celiac disease, but there was a chance it could tell us once and for all if she did not have it. We wanted to know so we said, ‘Okay, let’s try it.’”
Ruling It Out
The genetic test for celiac disease focuses on two particular markers—HLA-DQ2 and HLA-DQ8.
“Ninety-nine percent of celiacs have either HLA-DQ2 or HLA-DQ8,” says Alessio Fasano, MD, medical director at the University of Maryland Center for Celiac Research.
Human leukocyte antigens (HLA) are proteins, of which DQ is a subset, that are found on the surface of almost every cell in the body and are a key component of the immune system. While everyone has slightly different HLA proteins, each of us has two sets, one inherited from each parent.
The snag with the genetic test is that having DQ2 or DQ8 doesn’t mean you have celiac or that you’ll ever develop it. In fact, up to 40 percent of the population has one of these markers and very few of these people will ever get celiac disease.
“There’s no predictive value of developing celiac with DQ2 or DQ8,” explains Fasano. Instead, it’s the absence of the DQ2 or DQ8 marker that’s useful information. Because the chances of developing celiac disease without having either DQ2 or DQ8 are extremely low, Fasano says that “the proper use of the genetic test is to rule out celiac disease.”
There’s little gain in testing someone already diagnosed with celiac, he says. Some celiacs elect to have the test out of curiosity but “for a biopsy-diagnosed celiac, it’s not a value-added test. The genetic information doesn’t change anything about their disease or treatment.”
But there are definite indications for undergoing genetic testing. Three different groups of people can benefit most.
1] Perhaps the largest group is the first-degree relatives of a celiac. These people are at risk of developing the disease, says Fasano, who regularly recommends screening family members with both HLA genetic testing and serological blood tests.
“HLA typing can determine whether doctors should keep an eye on an individual or not,” Fasano explains. “If the individual has a negative test result, the chances of developing celiac are low.”
For Jenna Farley of New York City, it was a relief to discover her newborn son didn’t carry the celiac gene. “I was diagnosed with celiac disease five years ago. When my son was born, I had him tested when he was just a week old,” Farley says. “My two sisters were tested and they both have the DQ2 gene. Now they know to be screened regularly for the disease.”
2] The second group that might consider genetic testing are individuals with medical conditions frequently associated with celiac disease, says Fasano. That includes patients with autoimmune conditions, such as Type 1 diabetes, thyroid disease and Addison’s disease, as well as certain genetic disorders, such as Down’s syndrome.
3] The third group is made up of patients like Abby who are struggling to find a diagnosis and want to know if their symptoms are due to celiac disease or gluten sensitivity.
“This group of patients is not insignificant,” says Fasano, “They may have suffered for years from ataxia [clumsiness symptomatic of a neurologic condition], brain fog or depression without a satisfactory diagnosis. At some point, they may have read about celiac disease and may have given the gluten-free diet a try. In many cases, their symptoms improve on the diet. But because celiac disease requires a 100 percent lifelong commitment to the diet, they want to know where they are on the spectrum of gluten sensitivity. The test can help distinguish if their symptoms are due to celiac disease or gluten sensitivity.”
Perhaps the biggest advantage of the genetic test is that, unlike a blood panel or small intestinal biopsy, being on a gluten-free diet will not alter test results. Gluten-sensitive patients who cannot—or will not—tolerate a gluten challenge (the temporary reintroduction of gluten to the diet) may opt for the genetic test to rule out the disease.
Counting the Cost
One question Williamson had about the genetic test was the price. She worried the test would be prohibitively expensive.
“There’s a perception out there that genetic testing costs a lot,” says Carol Shilson, executive director of the University of Chicago Celiac Disease Center. “The methodology used to be much pricier than it is today. Newer technologies have made it less expensive.”
Depending on the lab, the cost can range from $350 to $800. A significant variable is how in-depth the testing is.
“It’s really important that the lab look for the half heterodimer on the DQ2 gene,” says Shilson. The DQ2 gene can be divided into two components, called alpha (DQA1*05) and beta (DQB1*02) subunits. Not all labs look for both parts.
According to the National Institute of Health’s Human Genome Project, more than 1,000 genetic tests are available today. Shilson recommends selecting a lab that specializes in celiac disease.
“There are huge labs out there running hundreds of genetic tests but they don’t necessarily know the specifics of celiac genetics,” she says. “We’ve seen patients use labs that offer the genetic test for celiac and sometimes the labs are not using accepted science or they outsource the testing. In these kinds of cases, we’ve seen results reported incorrectly.”
Importantly, labs that specialize in celiac genetics are more likely to stay current with the latest research and technology specific to the disease. While DQ2 and DQ8 remain the most important genes for the genetic test, recently nine other genes associated with celiac disease were discovered, as reported at the 2009 International Celiac Disease Symposium held in Amsterdam in April 2009.
Abby’s genetic test cost approximately $500. With preauthorization from the doctor’s office, insurance covered most of the cost. “A welcome surprise,” Williamson says.
While a genetic test need never be repeated (genetic information doesn’t change), the cost can be high if many family members are to be tested. To assist with this, some labs offer discounts for multiple orders.
Unlike other genetic tests, privacy isn’t a big issue for celiac testing.
“We didn’t really worry about the implications,” Williamson says.
She’s not alone. Shilson says most patients at the University of Chicago Celiac Disease Center aren’t terribly concerned. “The genetic test for celiac disease is different from many other genetic tests,” says Fasano. “A positive result doesn’t imply much. It has little predictive value on the lifetime risk of developing celiac disease.”
What’s more, a recent federal law helps address concerns about the misuse of genetic information.
The Genetic Information Nondiscrimination Act of 2008 (GINA), protects Americans from being treated unfairly due to DNA and health issues. The new law, which went into effect in November 2009, prevents discrimination from health insurers and employers. Its protection does not extend, however, to life insurance, disability insurance and long-term care insurance.
Shilson says that patients concerned about privacy and potential misuse of information often elect to circumvent insurance companies by paying for genetic testing out-of-pocket.
Your Genes, Please
For her genetic test, Abby gave a small sample of blood, drawn at a nearby lab, “It was really easy. They just took one tube of blood. No special preparations were necessary,” Williamson says.
Newer tests offer in-home convenience without the needle. Genetic material can now be extracted from cheek cells or saliva.
“A new test examines samples obtained by wiping the inside of the cheek several times with what looks like a mascara wand,” explains Shilson. “It’s done at home and mailed to the lab in the kit provided to you.”
Just as easy, a saliva test requires that patients spit into a small tube and then drop it in the mail.
“While its best to do genetic testing through your doctor, if your physician isn’t supportive and you’ve hit a wall, it’s possible to order the kits directly from the laboratories,” says Shilson. Labs provide results to the patient or the doctor, or both. An advantage of going through your doctor is that he or she can help interpret the results. However, Shilson adds, the labs have excellent genetic counselors on call.
Though newer tests may be more convenient, many patients like Abby use whatever sampling method is covered by their insurance. In many cases, an insurance company will stipulate a blood panel, not because it’s more accurate but because the company is behind on changing technology.
“The methods covered by insurance don’t necessarily speak to the accuracy of the newer tests,” Shilson says.
After Abby’s blood was drawn, the sample was shipped overnight to a lab to begin the complex genetic analysis. Some genetic tests are turned around in just a day or two. The lab that Abby used took a bit longer. The results? She was positive for the celiac gene.
For Williamson and Abby, who had hoped the test would conclusively rule out celiac disease, the results were disappointing. But as Williamson acknowledges, “That’s the reality of the test. I’m glad we did it because if not, we would have wondered.” The test provided another useful data point and, “For us, it was part of the journey to get Abby well,” Williamson says.
After learning the test results, Abby resumed the gluten-free diet. Although the positive read didn’t mean the diet was necessary for her, it seemed prudent to give it a second try. In addition, she cut out soy and dairy at the suggestion of her gastroenterologist.
Eliminating dairy made a huge difference. “It may be the reason why Abby didn’t feel 100 percent better the first time she went gluten free,” Williamson speculates. “We still don’t have a formal diagnosis. As best as we can tell, she is sensitive to gluten, dairy and soy.”
Now 13, Abby has no complaints when it comes to her health. She is happily back on the soccer field—without the frequent bathroom breaks. Co-captain of the team, she recently received the female athlete of the year award at her middle school.
She’s also becoming quite accomplished in the kitchen, learning to bake gluten, dairy and soy free.
“Recently, we spent the whole morning together making blueberry muffins, oatmeal cookies and bread. It was a lot of fun,” Williamson says. “Eating used to cause Abby so much pain. It’s wonderful to see her finding joy in food again.”
Christine Boyd is a freelance writer who lives in Baltimore.