For much of human history, many genetic disorders were accepted as incurable, their rapid onset bound to take patients’ lives before they had the chance to be lived.  However, the 21st century has been a golden age of progress that is shocking the medical world with treatments never before considered possible.

As originally reported in Healthline, a collaborative effort between doctors in Saudi Arabia, France, and the United States saved a child born with USP18, a genetic disorder that causes extreme inflammation which typically robs patients of their life within weeks. The rare disorder required transcontinental collaboration to gather the various niche technologies and top level expertise. With remarkable success, the patient was quickly matched with a rare drug, allowing him to continue to live in remission. He is now age 3. 

USP18

USP18 is a disorder with a characteristically early onset. The genetic mutation damages protein production, causing inflammation that is so severe that by the time the baby has reached a couple weeks of life, they are overcome by severe inflammation across the body which causes difficulty to breathe and the accumulation of liquid in the brain. While the inflammations appear to be more common infections, they do not respond to treatment options. The ultra-rare disorder affects about 1 in a million people.

The disorder, like many other rare diseases, has an incredibly rapid timeline before the inflammation overtakes the body’s ability to function. This means time is of the essence. This type of disorder is particularly difficult to treat because it requires rapid diagnosis, expensive technology, specialized expertise, and rapid access to individualized medications to pull off. As told to Healthline, Dr. Dusan Bogunovic, who was part of the team from the Icahn School of Medicine at Mount Sinai in New York, explained just how vital the joint effort was to curing the patient. Bogunovic said,

 “I don’t think this can be stressed enough, rare diseases by definition cannot be managed alone. Each requires expertise that very few people on the planet have.”

Swift International Medical Collaboration

The doctors who came together on the case attribute their success to their collaborative efforts. The baby was being cared for by physicians at King Saud University in Saudi Arabia, where the doctors prevented the worst of the inflammation, keeping him alive months after birth. Still, they knew it would take more than that for him to live much longer, and knowing it was a inflammation-related genetic disorder, they got in contact with physicians in New York who specialize in rare inflammatory disease research.  So the partnership began, and they figured out how they could put their abilities and technology together to find a diagnosis and treatment plan.

Diagnosis: Genetic Sequencing

The New York team immediately set to genetic sequencing. They suspected the disease to be related to the exons: a critical part of DNA which codes for proteins. The doctors ran tests for exome sequencing, which only sequences the region which is responsible for coding proteins. This new type of exome sequencing or whole genome sequencing is more advanced than the traditional methods. This is important for diseases like this one which have a rapid onset and must be identified immediately. They identified a very rare genetic mutation of the ubiquitin-specific peptidase 18 gene, which plays a role in regulating inflammation.

This method of diagnosis is causing great excitement in the field as a cheaper, faster alternative to previous options. While not cheap, the cost is mediated by the immediate answers many patients need. It can, as it did in this case, identify the mutated gene responsible for the disorder and immediately get to the next stage of treatment. Many diseases could have their impact lessened if caught before progressing, but rare disease diagnosis is notoriously difficult and the experts are few and far between. Patients run in circles for years while racking up expenses.

Finding a Treatment

Once they identified the mutation, the doctors were tasked to find an appropriate treatment. There was no available treatment option that they knew would work. After experimenting with a few different anti-inflammatory drugs and trialing which was best suited, they found success in the oral treatment ‘ruxolitinib.’ Upon receiving this treatment, the boy began to show signs of improvement in just weeks. He continued to receive the treatment for the following years, and today he lives without symptoms of the condition.

This success is a novel feat that was only possible because of rapid, high skill maneuvering to keep him alive as they identified the disease and sought treatment options. The deficiency that is usually unstoppable was stopped due to  high level collaboration. The New York team had this to say:

“We showed that even with a disease like USP18 deficiency, sound clinical care and timely drug administration can rescue patients from what was previously considered a death sentence. The teamwork between our two institutions and others around the world is a textbook case of science without borders.”