A Call for Precise Rare Disease Definitions

No one knows how many rare diseases there are and that’s a problem because it’s likely that many rare disease patients do not receive appropriate medical care, according to University of New Mexico data scientist Tudor Oprea.

In a commentary published in Nature Reviews Drug Discovery, Oprea and colleagues from the United States, Australia, France, and Germany point out that as much as 10 percent of the world’s population suffers from a rare disease, which translates into hundreds of millions of people.

“You have thousands and thousands of papers a year related to rare diseases, yet very few translate into cures,” says Oprea, professor and chief of the Translational Informatics Division in UNM’s Department of Internal Medicine.

Definitions are a big part of the problem because the inability to reliably diagnose a rare disease hinders researchers’ ability to develop treatments for it, write the authors.

The Orphan Drug Act of 1983 defines a rare disease as one affecting fewer than 200,000 people in the United States. In the European Union, legislation introduced in 2000 defines rare disease as a disorder affecting fewer than one in 2,000 people.

But, the authors say, a disease that is considered “rare” in the general population might be relatively common within a subgroup, such as Tay-Sachs disease among Ashkenazi Jews or sickle cell disease among people of sub-Saharan African descent.

Another complicating factor is that the terms used to define diseases are often inconsistent and imprecise, and they sometimes vary from country to country. For example, “breast cancer” actually encompasses a variety of tumor sub-types with unique genetic signatures and different optimal treatments, said Oprea. Should it be classified as one disease or many?

Estimates of the number of rare diseases usually settle in the range of 7,000, the authors report. But their recent analysis of an international disease classification database known as the Monarch Disease Ontology—or Mondo—suggests it could be as much as 50 percent higher.

“The Mondo project is the first computer-assisted human curation process to bring together separate efforts in the rare disease community in order to catalog and annotate all rare diseases, regardless of country or disease type,” Oprea said.

Improving care for patients with rare diseases requires reaching consensus on the physical, genetic, and environmental characteristics of each condition, but overlapping terminologies and models makes that difficult, noted the study authors. They call on the World Health Organization, the U.S. Food and Drug Administration, the European Medicines Agency, the National Academy of Medicine, and other entities to adopt a unified definition of rare diseases.

“We encourage the community to get together and come up with more precise rare disease definitions,” Oprea said. “There needs to be a forum to discuss this and dedicated funding mechanisms to address it.”

Photo: Tudor Opera, University of New Mexico data scientist

Author: Rare Daily Staff