A new path forward: Hussein
From the beginning of Hussein’s life, a shroud of worry surrounded him. Something was wrong. The infant couldn’t keep down anything he ate. When he was 6 weeks old, his mother, Manal, noticed blood in his stool. He lost precious weight and was hospitalized due to failure to thrive. Hussein’s first few months were defined by medical tests, painful procedures, and uncertainty.
“You name it, they tested him for it,” Hussein’s father, Ali, says. “They put a feeding tube through his nose. He was hospitalized for 20-plus days. He really went through a lot. As a baby, he couldn’t tell us, but you could just look in his eyes and see.”
Doctors identified Hussein as having duodenitis, an inflammation of the first section of the small intestine, and diagnosed him with inflammatory bowel disease (IBD). With medications to treat the intestinal inflammation and a strict diet of hypoallergenic baby formula, Hussein gained weight and was released from the hospital.
For the next eight years, several times a year, the family made the nearly three-hour drive from their home in northern Ohio to Cincinnati for specialist visits to monitor Hussein’s inflammation, which varied in location and intensity.
“We were driving all the time, going back and forth,” Ali says. “They did two lower and two upper GI scopes. It was hard having him go under anesthesia all of the times for the different tests, and we couldn’t give him anything to eat. We continued to get stool samples. It was eight years of hell.”
Through it all, Manal and Ali wondered if their child had been correctly diagnosed. They also wearied of the long-distance trek and sought medical care closer to home.
In 2019, Hussein’s new pediatric gastroenterologist informed Manal and Ali about a test recently developed and implemented by Mayo Clinic Laboratories that might provide clarity on what was triggering Hussein’s IBD.
“We went along and did the test,” Ali says. “That is when we found out he had familial Mediterranean fever.
"I can’t even describe in words what this test did for us. It gave us a lot of relief. The test was wonderful because we knew what he had.”
The Mayo Clinic Laboratories test that Hussein received (Mayo ID: IBDGP) uses next-generation sequencing to evaluate specimens for variations in more than 50 genes with known association to monogenic IBD-like conditions, such as familial Mediterranean fever.
While familial Mediterranean fever can cause symptoms similar to those of IBD, it is an inherited autoinflammatory condition that causes recurrent fevers and painful inflammation of the abdomen, chest, and joints.
“The main issue was that this particular patient presented with a phenotype that looked like IBD,” says Ann Moyer, M.D., Ph.D., who helped process Hussein’s test at Mayo Clinic Laboratories. “Usually if someone is thinking about IBD, those tend to not be monogenic disorders. But if it presents at an early age, it could be due to a different monogenic disease that presents like IBD. It can get tricky, particularly in the pediatric setting.”
Within the field of gastroenterology, it’s long been accepted that ulcerative colitis and Crohn’s disease are the primary forms of IBD. However, for a subset of patients who present with symptoms earlier in life, alternate disease states are being considered as the root cause of the gastrointestinal symptoms.
“IBD is a very complex disorder,” Dr. Moyer says. “In general, when it presents in younger children, these are the patients with this diagnostic dilemma of, is it classic IBD or something that needs some other treatment? It’s a newer concept in GI that there are different disease processes that resemble IBD."
“The reason that it’s so important to figure out what it is,” Dr. Moyer continues, “And identify the subset of diseases that look like IBD but aren’t, is that patients typically respond to different treatments.”
Indeed, following Hussein’s 2019 diagnosis of familial Mediterranean fever, he ceased taking specialty-compounded IBD medication and instead received colchicine — a medication that disrupts regulation of multiple inflammatory pathways.
The family noticed immediate improvement. His pediatric gastroenterologist transferred Hussein’s treatment to a rheumatologist. Under careful monitoring by his local care team, Hussein’s inflammation decreased to normal levels, and he was removed from all medications.
“It means a lot to us, not only what this test did, but all of the research done at Mayo Clinic to come up with this test. We appreciate it,” Ali says. “We hope it helps other families who are going through the same thing we did.”
While familial Mediterranean fever occurs most commonly in individuals of Armenian, Arab, Turkish, and Sephardic (non-Ashkenazi) Jewish ancestry, the diversification of the world’s population has meant the illness appears in individuals of all ethnicities. Because the condition usually follows an autosomal recessive inheritance pattern, an individual needs to get a copy of the affected gene from both parents to develop the condition.
“Even though we call it Mediterranean fever, not only patients from the Mediterranean can have pathogenic genetic variants. People from other backgrounds also can have these variants,” Dr. Moyer says. “That’s the thing to think about, especially in the U.S. where we have a diverse population, and the world is so much more globalized than it used to be.”
Typically, patients who have variants linked to monogenic illness rather than classic IBD are those who do not respond well to conventional therapy or whose symptoms develop early in life.
Although the test went live at Mayo Clinic Labs in 2018, it’s been ordered less than 200 times. “I think the test is probably underordered still at this point in time,” Dr. Moyer says.
“It’s only been within the past five to 10 years that people have been doing a lot of research in this area and realizing a lot of these cases are due to monogenic genetic disorders.”
And while the test doesn’t always detect a genetic variant as the cause of a patient’s illness, quite a few patients like Hussein have received positive, life-altering results.
“In young patients with IBD or patients who are older who don’t respond to therapy appropriately, sometimes we can identify a different reason for their symptoms that requires a different treatment course, and that can improve their outcome,” Dr. Moyer says. “When you can actually make a big difference like that, it’s always a test to be proud of.”