What is Otulipenia? Scientists Discover Rare Fatal Inflammatory Disease Affecting Children

Scientists from the National Health Institute have discovered a rare and sometimes fatal inflammatory disease that can affect children, causing fever, skin rashes, diarrhea, joint pain and overall failure to grow and thrive.

The newly discovered disease, dubbed as Otulipenia, is an inflammatory disease that occurs when genes that is part of a person's innate immune response mutate, which could trigger the immune system to launch as an attack to the body's own tissue.

The discovery was made after the researchers identified four children from Pakistani and Turkish families with unexplained skin rashes and joint pains. Using next-generation sequencing technology, the researchers discovered that the OTULIN gene of the sick children were abnormal. OTULIN is responsible for regulating the development of new blood vessels and mobilization of cells and proteins to fight infection.

After studying the immune pathway of the children, NIH scientists discovered that the problem lies in the inability of the children to remove ubiquitin proteins, a small protein that regulates many other proteins in the body, including immune molecules. When the body is unable to remove ubiquitin proteins from various molecules, the production of chemical messengers were increased, resulting to an infection.

"The malfunction in this protein has not been previously linked to clinical disorders of the human immune system," explained Ivona Aksentijevich, M.D., staff scientist in NHGRI's Medical Genetics Branch and co-author of the study, in a statement. "This discovery suggests a direction that can be explored for development of new therapies for patients with a wide range of inflammatory diseases."

After discovering the increased production of chemical messengers, the researchers tried to treat the abnormality using a drug that inhibits tumor necrosis factor, a chemical messenger involved in systemic inflammation. Children treated with the anti-tumor necrosis factor (TNF inhibitors) showed improvement.

With their findings, the researchers suggested a new category of human inflammatory diseases caused by impaired ubiquitination. Furthermore, the result f their study could also provide a direction that can be explored to develop new therapies for patients with a wide range inflammatory diseases.