Lethal Inflammatory Disease: Otulipenia

Researchers from the National Institutes of Health, along with colleagues in Turkey and the UK, have discovered a rare and sometimes lethal inflammatory disease that primarily affects young children. Known as otulipenia, the condition can involve joint pain, rashes, fever, and growth problems.

As indicated in the September 7, 2016 news release, “Otulipenia is caused by the malfunction of OTULIN, a single gene on chromosome 5. When functioning properly, OTULIN regulates the development of new blood vessels and mobilization of cells and proteins to fight infection…”

The researchers determined that the children with otulipenia might respond to drugs that turned off tumor necrosis factor, a chemical messenger involved in systemic inflammation. Inflammation subsided in the children who had been treated with anti-tumor necrosis factor drugs (TNF inhibitors). TNF inhibitors are also used to treat chronic inflammatory diseases such as rheumatoid arthritis.

“The results have been amazing and life changing for these children and their families, ” said Daniel Kastner, M.D., Ph.D., co-author, NHGRI scientific director and head of National Human Genome Research Institute’s (NHGRI) Inflammatory Disease Section. “We have achieved the important goal of helping these young patients and made progress in understanding the biological pathways and proteins that are important for the regulation of the immune system’s responses.”

Ivona Aksentijevich, M.D., staff scientist in NHGRI’s Medical Genetics Branch and study co-author, told OTW, “We are a major referral center for auto-inflammatory diseases and as such we see patients or receive patient DNA samples from all over the world. We have a very good (or considerable) reputation in gene discoveries and our colleagues like to refer their undiagnosed cases to our clinic for research studies. We did not speculate that OTULIN could be a candidate gene for auto-inflammmatory diseases. It was by pure genetic analysis that we discovered disease-causing mutations in this gene in three patients from our cohort. This study also shows how international collaborations are very important when studying patients with rare diseases.

“It takes a village to define a new disease, but it is very exciting when it happens. Especially, when the understanding of the disease pathogenesis can point to therapies that are already available. We have seen our patients grow off steroids and the smiles on their faces at being able to live almost normal life. That is not the case just with this disease but with many other diseases that have been discovered during the past 20 years as the result of genetic studies and human genome project. They are rare diseases but collectively we are talking about hundreds if not a thousand of children. In addition, with the discovery such as otulipenia, pharmaceutical companies have now the new target pathway to consider for development of anti-inflammatory drugs.”