In mid-December, Kareena Hijjawi, a fifth grader from Roseville, California, and her mother, flew to the National Institutes of Health, their second trip this past year. After settling into their room at the Children's Inn at NIH, on the Bethesda, Maryland campus, Kareena and her mother began a series of important clinical consultations at the nearby NIH Clinical Center. Kareena is enrolled in the pediatric component of the NIH Undiagnosed Diseases Program (UDP), part of the Undiagnosed Diseases Network.
Yet the trip wasn't totally dominated by stethoscopes and blood tests. Before the week was out, Kareena would be flocked by dancing ballerinas and dazzled by the opulence of the White House Holiday Tour. She would even have the rare opportunity to pet the Obama family dogs, Sunny and Bo.
Kareena's recent travels had their beginnings seven years ago with a medical journey that started at age three. Kareena began experiencing symptoms of an illness that her doctors couldn't diagnose. She was first hospitalized in 2007, during an extended visit to Jordan, her father's home country. She had a fever, difficulty walking, muscle stiffness and skin rashes.
Her unexplained symptoms have worsened over the past three years. After a fall in 2012, she was rushed to the hospital emergency room and underwent cranial imaging. That's when doctors detected calcifications in Kareena's brain. Yvonne Wu, M.D., professor of clinical neurology and pediatrics at the University of California, San Francisco School of Medicine, saw the brain scan results and contacted Camilo Toro, M.D., a neurologist with the UDP, who studies brain calcification. As a result, the UDP accepted Kareena's case. Each year, the program accepts about 50 children who have illnesses that are among the most difficult to solve. Cases are referred to this six-year-old NIH program only after doctors elsewhere have been unsuccessful in reaching a diagnosis.
During an initial UDP visit to the NIH Clinical Center in January 2014, Kareena received many evaluations and consultations from a multi-disciplinary group of clinical researchers. NIH researchers performed a molecular study called whole-exome sequencing that required a DNA sample from Kareena, her parents and her five siblings. Exome sequencing explores the 1-2 percent of the genome that codes for proteins, the most likely place to find DNA differences that could cause or contribute to disease. The participation of immediate blood relatives in exome sequence studies helps researchers detect genomic variants - specific points of difference in the genetic code - by comparing the genomes of family members.
In addition to Dr. Toro, the UDP team included Cynthia Tifft, M.D., Ph.D., director of the pediatric UDP, Thomas Markello, M.D., Ph.D., staff clinician in NHGRI's Medical Genetics Branch and Gretchen Golas, CRNP, a pediatric nurse practitioner and the admitting NHGRI clinician for Kareena's inpatient stay. Kareena's comprehensive evaluation included consultations with immunologist Raphaela Goldbach-Mansky, M.D.; ophthalmologist Wadih Zein, M.D.; rehabilitation physician Scott Paul, M.D.; dermatologist John DiGiovanna, M.D.; neuropsychologist Audrey Thurm, Ph.D.; and clinical geneticist David Adams, M.D., Ph.D.
Based on the exome sequencing data, the UDP team diagnosed Kareena in September 2014 with Aicardi-Goutieres Syndrome, type 7. Aicardi-Goutieres syndrome is a rare neurological disease usually detected in childhood that causes an autoinflammatory response in the brain and skin. It can occur due to mutations in a number of different genes. Exome sequencing showed that Kareena's DNA has a variant in the IFIH1 gene that was not passed down by her parents, but is a new, or de novo, gene variant. The variant causes an overproduction of interferon, a protein that plays a role in infection response. "Fortunately, there is ongoing research to study this disease," said Ms. Golas, who cared for Kareena during her initial evaluation in January 2014, and notified parents Heather and Ayman Hijjawi of Kareena's diagnosis with a phone call. She also planned the December follow-up visit when the UDP team discussed Kareena's diagnosis and provided genetic counselling.
Kareena may be eligible for a clinical protocol led by Adeline Vanderver, M.D., director of the Myelin Disorders Clinic at Children's National Health System, said Ms. Golas. The knowledge of a diagnosis and the prospect for possible treatment has given the Hijjawis hope.
"It was nice to get answers," Ms. Hajjawi says of the NIH Clinical Center visit. She also recognized that the medical follow-up can be difficult for a 10 year old and that Kareena might enjoy a few outings during their trip. With some forethought, she ordered tickets via her congressional representative to tour the festive holiday trimmings at the White House. The theme of this year's décor is, "A Children's Winter Wonderland."
"The White House is gorgeous this time of year," said Ms. Hijjawi. "Kareena really liked the Red Room."
But since the tour included climbing a staircase and Kareena is in a wheelchair, the Hijjawis were escorted to an out-of-the-way elevator. During their wait, two furry occupants of the mansion came bounding down the hall toward Kareena. "Kareena was hoping to see President Obama. That didn't happen, but she did get to pet his dogs, Sunny and Bo," said Ms. Hijjawi.
The Hijjawis also attended a performance of Tchaikovsky's The Nutcracker, the majestic ballet performed by members of the American Dance Institute in Rockville, Maryland. Kareena, who was not sure what to expect of the performance, became a bit worried that the curtain wouldn't rise for the second half of the show.
"It was just amazing to watch the faces of the kids light up," said Ms. Hijjawi. Afterwards, the performers mingled with their NIH guests during a cookie social.
While on the way to the airport for their return trip, Ms. Hijjawi asked Kareena to name her favorite part of her eventful trip to NIH. Kareena replied, "Spending time with you."
Posted: December 22, 2014