Missed diagnosis has devastating consequences

February 4, 2020

What caused a sociable teenager to transform like the Hulk?

Matthew Khorana has returned to his outgoing nature

By Amy Ratner, Medical and Science News Analyst

The transformation Matthew Khorana suddenly went through at 17 reminded his mother Melissa of watching the Hulk, the fictional soft-spoken scientist who becomes a green monster powered by uncontrollable rage.  Matthew, who has Down syndrome, had always been sociable, happy and caring, with a love of Power Rangers and Goosebumps and acting out his favorite TV shows and movies.

But almost overnight, he started exploding into a menacing and aggressive stranger.

He once punched his mother in the face at a birthday party and another time became so violent that one of his three younger brothers was frightened enough to call the police.

Symptoms hold the clue

These symptoms were eventually attributed to anxiety and depression in a young adult with Down syndrome, says his mother. He was prescribed multiple psychiatric medications, which muted his personality and caused him to gain 85 pounds but did not completely control his outbursts.

Along with the sudden change in his personality, Matthew had abdominal pain, nausea, weight loss, and eventually diarrhea, incontinence and blood in his stool. He was seen by seven doctors from various specialties, including gastroenterologists, before being “handed off” to psychiatrists and psychologists.  He had repeated endoscopies, but everyone missed what was really wrong with Matthew.

It took seven years for a doctor to finally get his diagnosis right, and nearly that long for his mother to get over her anger about what had happened to her son and the rest of her family to be able to tell his story.

Melissa, a nurse practitioner, and Matthew’s father, Alok Khorana, MD, did so recently in an opinion piece published in the Journal of the American Medical Association.

Life changing diagnosis

When the family moved from Rochester, NY, to Cleveland, OH, they found the primary care physician who looked over the long list of Matthew’s symptoms and medications and said the words that changed life again for Matthew and his family’s life.

“’I’m pretty sure he has celiac disease,’” Melissa Khorana recalls the doctor saying at Matthew’s first visit. Celiac disease blood tests and a biopsy confirmed the diagnosis and Matthew started a gluten-free diet.

Within months, he was off most of the medications, his outbursts nearly stopped, he lost weight and his gastrointestinal symptoms improved. Today, as he approaches 30, Matthew is healthy and living semi-independently. “Gluten” is one of the words he knows, and he looks for “gluten free” on food packages.

Neurocognitve symptoms

Matthews story illustrates the ways in which neurocognitive symptoms of celiac disease are often misinterpreted, leading to incorrect diagnosis. And it demonstrates the complexity of diagnosing celiac disease because gastrointestinal symptoms and behavioral problems are also common in Down syndrome.

Neurocognitive: decreased mental function due to a medical disease other than a psychiatric illness

“This is a complex issue, but the truth is celiac disease is a serious autoimmune disorder with a myriad of symptoms, including neurocognitive symptoms,” says Alice Bast, Beyond Celiac chief executive officer. While Matthew’s symptoms were severe, many celiac disease patients report a constellation of issues with brain fog, spatial problem solving, detachment, depression, anxiety, irritability, low energy, impaired speech and problems with sleep, memory and orientation to time and place, a Beyond Celiac study found.

Related: Beyond Celiac study of neurocognitive symptoms in celiac disease

“When we look back at the seven years of misdiagnosis, and the burden it placed on our growing family, it is with a mixture of sadness, anger, frustration and guilt,” the Khoranas wrote. They hope by sharing Matthew’s story they can save others from the tortuous experience he had.

Down syndrome and celiac disease

Although research into the relationship between Down syndrome and celiac disease was scant as late as the 1990s, studies in 2018 and 2019 show three to six percent of those with Down syndrome have celiac disease compared to one percent in the general population.

Diarrhea, constipation and other stomach conditions, as well as growth impairment and anemia are frequent in Down syndrome itself, making it harder to recognize that they may also be signs of celiac disease. The story is similar for when it comes to behavioral change.

The National Down Syndrome Society says at least half of all children and adults with Down syndrome face a major mental health concern during their life, which could prevent neurocognitive symptoms from being attributed to celiac disease. The National Down Syndrome Congress estimates depression and other forms of mental ill health affect about 20 percent of young adults with Down syndrome, an amount about equal to the general population. A 2017 study found that psychological and psychiatric dysfunction is a major problem in a substantial proportion of young adults with Down syndrome.

Even patients who are treated through Down syndrome programs in the United States are not screened for celiac disease as often as needed, a 2016 study of five Down syndrome specialty centers found. The study concluded that celiac disease is an important consideration in the comprehensive care of individuals with Down Syndrome, but although symptoms are common, diagnoses are infrequent. The study noted that the symptoms most commonly reported to specialty providers were persistent constipation and behavioral problems that did not respond to usual treatment.

Related: Celiac Disease and Down Syndrome

Matthew was treated as though he had behavioral issues versus a medical condition, according to his mother. “I knew in my gut that it had to be something medical the way it came on, and that was dismissed,” she says. “When you have a child with a disability, people sometimes treat you like you are trying to live in ideal world and not deal with what the reality is, like I was supposed to accept that that’s just who Matthew was going to be.”

Need for screening

The overlap in symptoms and the high prevalence of celiac disease point to the need for routine screening for celiac disease, studies show.  The celiac disease guideline committee of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) recommends celiac disease screening in children with Down Syndrome even when they have no symptoms, while the American Academy of Pediatrics recommends testing in children only when they have symptoms.

A 2017 study of screening for celiac disease among those with Down syndrome noted late diagnosis can lead to sometimes severe complications. “Many medical organizations recommend screening in this group of patients,” the study says. “However, current policy statements vary in their recommendations for screening and there is still a need for establishing uniform diagnostic criteria.”

Melissa Khorana agrees that more awareness of celiac disease and screening for it are needed. The connection with Down sydrome is better recognized now than it was when Matthew was diagnosed, which happened because his new primary care doctor was following related studies. But his mother suspects it’s still not well known in many places in the United States. She notes that only about .4 percent of the population has Down syndrome, so it is hard to find experts in the field. Consequently, those with Down syndrome are treated by primary care doctors to whom information about the connection with celiac disease has not trickled down from areas with specialists. “When I tell my story of what Matt has gone through, people are so surprised,” she says. “I hear so many times, ‘I did not know celiac disease could do that.’ Well it can and it did.”

It’s doubtful that even gastrointestinal symptoms, which are much more widely recognized in celiac disease than neurocognitive symptoms, would regularly lead to celiac disease testing, Melissa Khorana says. “A doctor who is out in the community, no, I doubt it would be the first thing on their radar,” she notes.

Matt’s back

Before Matthew was diagnosed, his family was on edge all the time not knowing when he might have an episode. They were afraid to go out to eat, to go on vacation. “We withdrew because we were afraid to go out in public,” his mother says. But today, the family is able to travel together and enjoy each other’s company again. “We say, ‘Matt’s back,’” Melissa Khorana explains. Even his love of Goosebumps returned.

Now she feels it’s time to tell his story to spread awareness about celiac disease and Down syndrome. “It was such a simple thing that could have been taken care of years earlier,” she says.

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