USP18 deficiency is a rare genetic disorder that affects inflammation. It occurs in fewer than 1 in 1 million births.

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Doctors from Saudi Arabia, France, and the United States collaborated to help a young baby boy with a rare genetic disorder. Getty Images

A child with a rare genetic disorder called USP18 would normally be expected to survive for no more than a few weeks.

But thanks to the collaborative efforts of physicians and researchers in Saudi Arabia, France, and the United States, a young boy with this disease is now 3 years old and in remission.

USP18 deficiency is a rare genetic disorder that affects inflammation. It occurs in fewer than 1 in 1 million births.

In a report published earlier this week in The New England Journal of Medicine, members of this international team describe how they used supportive clinical care, rapid genetic diagnosis, and prompt treatment with a novel anti-inflammatory drug to keep the boy alive.

Such collaborative efforts are very important for managing rare disorders like USP18 deficiency, Dusan Bogunovic, PhD, co-corresponding author of the case report and an associate professor of microbiology and pediatrics at the Icahn School of Medicine at Mount Sinai in New York, told Healthline.

“I don’t think this can be stressed enough,” he said.

“Rare diseases by definition cannot be managed alone. Each requires expertise that very few people on the planet have,” he continued.

Researchers in Bogunovic’s lab first described USP18 deficiency in 2016 as part of their work on rare inflammatory diseases in children.

They identified a very rare genetic mutation of the ubiquitin-specific peptidase 18 gene, which plays a role in regulating inflammation.

Mutations in this gene cause out of control inflammation that usually proves to be fatal in utero or shortly after birth.

“Babies [with USP18 deficiency] present with what appears to be an infection but don’t respond to antibiotics or antivirals,” Bogunovic explained.

“They have problems breathing. They have accumulation of fluid in the brain. They look like they are severely inflamed,” he continued.

The boy in Saudi Arabia developed these problems in the first weeks of his life. He didn’t recover after antibiotic and antiviral treatments.

After keeping him alive for months with supportive clinical care, physicians at King Saud University reached out to Bogunovic for help.

This was the start of a fruitful collaboration, in which experts across multiple institutions and countries worked together to rapidly develop a diagnosis and treatment plan.

To unravel the mystery of the boy’s symptoms, scientists conducted rapid genetic sequencing and protein testing.

These tests allowed the scientists to quickly identify a mutation in the USP18 gene that was interfering with protein function in the boy’s body.

Armed with this knowledge, they decided to try treatment with ruxolitinib. This oral drug belongs to a class of medications known as JAK inhibitors, which have potent anti-inflammatory effects.

After some trial and error, the boy’s treatment team found an effective dosage of the drug. Within 2 weeks, his symptoms began to quickly improve. Now, after 2 years of treatment, he remains symptom-free.

“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,” Bogunovic said in a press release.

“The teamwork between our two institutions and others around the world is a textbook case of science without borders,” he added.

This case highlights the role that rapid genetic diagnosis can play in the management of not just USP18 deficiency, but also in the management of other rare genetic diseases.

To find the mutation that was responsible for the boy’s symptoms in Saudi Arabia, Bogunovic’s team used a “next-generation” method of genetic analysis known as whole exome sequencing.

“Exome sequencing is a cost-effective DNA sequencing strategy that focuses on detecting genetic variants in the most critical regions of the human genome, the regions that contain genes and code for proteins,” Stephen Montgomery, PhD, an associate professor of pathology and genetics at Stanford University, told Healthline.

This method relies on new technologies that allow scientists to rapidly sequence all of the bits of DNA that provide instructions for producing proteins. Those particular segments of DNA are known as exons. Together, they comprise a person’s exome.

If a doctor or researcher wants to quickly sequence an individual’s entire genome rather than just the exome, they can use a method known as whole genome sequencing.

Together these methods of rapid testing have revolutionized the diagnosis and management of rare genetic diseases.

Compared to more traditional methods of genetic sequencing, whole exome sequencing and whole genome sequencing are much less time consuming.

And although these tests aren’t cheap, they tend to be less expensive than the battery of specialist appointments and lab tests that patients might otherwise need to get to the bottom of a mysterious illness.

“The way it used to work was, you’d go see a specialist and they would order a test, and you’d go see another specialist, and they would order a test — and since there are over 10,000 genetic diseases, you can imagine that that’s a lot of office visits,” Dr. Stephen Kingsmore, president and CEO of Rady Children’s Institute for Genomic Medicine at Rady Children’s Hospital in San Diego, California, told Healthline.

Instead of that long diagnostic odyssey, doctors can now order a single sequencing test to check for every known genetic disease.

“Instead of taking years to find out the rare genetic cause of a child’s condition, you can now decode their genome in a day,” Kingsmore said.

“Make an immediate diagnosis, nip the disease in the bud, and get the appropriate treatment on board immediately,” he said.