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Rare Genetic Disorder Drives Precision Therapy

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It got to the point that Jennifer Gleason’s 5-year- old daughter cried every time she had to leave her mother. Gleason, a single mother from Canyon, Texas, had been to so many doctors in so many cities, had so many operations and had been away from her three young children so much, that every parting felt traumatic.

What started as an out-of-the-blue seizure in 2017, progressed into a medical odyssey that included consultations with 16 different specialists; biopsies of her brain, lungs and bone marrow; and diagnoses ranging from stroke to cancer to immune deficiency.

Kanao Otsu, MD, MPH

In early 2018, Ms. Gleason’s breathing began declining rapidly. “I could hardly breathe. I could do nothing with my kids. I started feeling like I wasn’t going to be around for them.”

By the time she arrived at National Jewish Health, she had nodules throughout her lungs and a working diagnosis of common variable immune deficiency. While some symptoms and tests pointed to immune deficiency, others did not.

“Her story just didn’t make sense,” said pulmonologist Gregory Cosgrove,  MD, who saw Ms. Gleason first. So he consulted his allergy/immunology colleagues Kanao Otsu, MD, MPH, and fellow Amanda Grippen Goddard, DO, for an immunological evaluation.

Genetic sequencing of Ms. Gleason’s DNA, ordered by Drs. Otsu and Grippen Goddard, uncovered an extremely rare mutation to the CTLA-4 gene, which provided a much better explanation for her strange constellation of symptoms. The mutation causes a complex combination of both an overactive immune response and one lacking crucial elements to fight some infections.

Fortunately, there was a medication, abatacept, that was likely to work because it replaces the missing CTLA-4 protein. But abatacept is not approved for treating the CTLA-4 deficiency.

Insurance companies were reluctant to pay for the expensive medication. Dr. Grippen Goddard marshalled all the relevant literature and spent hours on the phone convincing two insurance companies that the medication was worth it.

Finally, in March 2019, Ms. Gleason began therapy with abatacept. And it is already working. Her lung function is improving. The nodules in her lungs and elsewhere in her body are rapidly resolving. Her energy has returned.

“This has been an extraordinary case, a perfect example of precision medicine,” said Dr. Otsu. “We discovered the exact genetic defect that was causing her disease and were able to treat it with a medication targeted at the malfunctioning protein.”

“This has been a godsend for me,” said Ms. Gleason. “I have hope for the future. And, I can play with my children again.”

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