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From Uganda to NIH, to Solve a Seizure Mystery

Posted on by Dr. Francis Collins

Ugandan family members in a conference room

Caption: From left, translator Irene Nakamya; Alice Alanyo and infant son Hassan Komakech; Concy Lamunu and infant son Jovan Lokpol; Balbina Lamon; Domasco Okenyy; and translator Tom Azalia during the Ugandan family’s visit to the NIH Clinical Center in May 2014.
Credit: Maggie Bartlett, National Human Genome Research Institute, NIH

In 2012, NIH researcher Avindra Nath traveled to Uganda to investigate a mysterious illness striking children between ages 5 and 15 in Acholi—a remote region in the north of that African nation. More than 3,000 children in Acholi and villages in nearby Southern Sudan were suffering from “nodding syndrome.” Named for the drooping, or nodding, head typically seen in patients, the condition is characterized by seizures, staring, and varying degrees of mental retardation.

Dr. Nath, a neurologist and clinical director at NIH’s National Institute of Neurological Disorders and Stroke, and Dr. Thomas Nutman, an expert in parasitic diseases from our National Institute of Allergy and Infectious Diseases, along with experts from the Centers for Disease Control and Prevention (CDC) and the World Health Organization, have joined with experts in Uganda to try to identify the cause of this disease. If you are wondering why the NIH would be interested in a mysterious syndrome seen in this region of the world, it is because any disease that spreads rapidly is a global threat.

Although CDC studies had ruled out the possibility that a toxin or infectious agent alone directly caused nodding syndrome, Dr. Nath decided to investigate whether infection with a parasitic worm called Onchocerca volvulus might trigger changes in the bodies of these children that set the stage for the disease. O. volvulus is endemic in the Acholi region and causes Onchocerciasis, or river blindness, through the bite of the blackfly. An estimated 25 million people in sub-Saharan Africa are infected O. volvulus.

Dr. Nath especially wanted to see if there were particular genetic variations that might make children more susceptible to nodding syndrome if they happened to become infected with O. volvulus. So, following a meeting with Dr. William Gahl, director of the Undiagnosed Diseases Program at NIH, Dr. Nath suggested to the Ugandan Ministry of Health that some of the patients come to NIH for studies that might explain the cause of the disease. The idea made sense, and arrangements were made to select an appropriate family and transport them to NIH’s main campus in Bethesda, MD.

NIH worked with the U.S. Department of State, CDC, and the Ugandan Ministry of Health to fly 10 members of an Acholi family, along with a Ugandan doctor and nurse, who also served as translators, to the United States. It was an enormous accomplishment. Members of this family had never been on a plane, slept in a bed, or owned a pair of shoes. They are used to tribal living; they speak a rare language (even by Ugandan standards), and eat a very different diet than Americans.

During their Washington trip, the three affected teenagers stayed at NIH’s Clinical Center, the world’s largest hospital dedicated to clinical research. When not in the hospital for testing, they and their family stayed nearby at The Children’s Inn, which is a private, non-profit home-away-from-home for families and patients participating in biomedical research or receiving treatment at the Clinical Center. The three teenage patients—ages 18, 17, and 13—underwent extensive medical testing, including detailed MRI imaging of their brains and overnight electroencephalography (EEG), which records electrical activity from brainwaves. In addition, all members of the family underwent a range of medical tests.

To investigate whether some of the children have genetic variations that make them more vulnerable to disease, Dr. Gahl also plans to sequence and analyze the exomes—the protein-coding part of the genomes—of all three affected children and their unaffected parents.

Dr. Nath’s current hypothesis is that antibodies the body generates to fight the O. volvulus worm also recognize a protein in the brain of vulnerable children and trigger the seizures. Thanks to the information collected during the family’s visit, Dr. Nath can now determine whether the data support this hypothesis, or lead to another conclusion.

Not only was the visit an unprecedented opportunity for biomedical researchers to learn more about a rare disease, it was a chance for both the Ugandan family and The Children’s Inn staff to learn more about each other’s worlds. To make the family feel at home, the inn’s nutritionists researched their traditional diet and prepared similar meals. Likewise, the family worked up the courage to try some foods that Americans love—like bagels with cream cheese!

Staff from The Children’s Inn also gave the family a whirlwind tour of the sights in nearby Washington, D.C. Though impressed by the U.S. Capitol, the Washington Monument, and other majestic landmarks, they were equally fascinated by all of the green trees—something not seen in the extremely hot, dry region where they live. And like most modern travelers, they quickly picked up the skill of documenting their activities by taking selfies—in this instance, using their guide’s mobile phone.

After two weeks of medical tests at the NIH and some memorable cultural experiences, the family flew back to Uganda last week. Dr. Bernard Opar Tolliver, who accompanied the family to the United States and is the coordinator of the nodding syndrome response at the Ugandan Ministry of Health, will remain the liaison between the NIH and the family.

Although we’ve collaborated with other countries to bring individuals suffering from rare disorders to NIH, we’ve never brought in so many members of a single family from so remote a region of the world. But the effort is worth it, because studying rare diseases can also lead to profound insights into common diseases. For example, in the U.S. alone, several million people suffer from seizures. Studying nodding syndrome could provide us with new insights about what causes seizures and new approaches to treating them.


Photos of the family from Uganda

Collage of images the family provided NIH during their visit—including their selfies.


NIH Undiagnosed Diseases Program (UDP)

Nodding Syndrome

Onchocerciasis (also known as River Blindness)

Avindra Nath, M.D.

William A. Gahl, M.D., Ph.D.

The Children’s Inn at the National Institutes of Health

NIH support: National Institute of Neurological Disorders and Stroke; National Human Genome Research Institute; National Institute of Allergy and Infectious Diseases; Common Fund



    Am grateful for what you doing to help my people of Northern Uganda
    God bless you

  • I.H. says:

    Excellent work. It’s heart warming to see the advances of medical sciences are at least now reaching to the remotest part of the globe – to the people who needs them the most.

    Initiatives like these must continue for the good of all Humankind.

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