Report finds thousands of uncounted rare diseases in challenge to current estimates

Have we been undercounting rare diseases? That is the question posed by nonprofit RARE-X, which has calculated that the low end of the oft-cited estimated range may miss half of all orphan indications. 

Reports about rare diseases typically cite one of two estimates. Some sources, such as the National Institutes of Health, state that there are around 7,000 known rare diseases. Other organizations, including the European Commission, quote a range of 5,000 to 8,000. Yet, those estimates have been knocking around for years, meaning that, even if initially accurate, they miss the hundreds of genetic diseases added to knowledge bases each year.

RARE-X dug into the two main international databases, Orphanet and the Online Mendelian Inheritance in Man, to try to come up with an accurate, up-to-date figure for the number of rare diseases. After trying to reconcile the two databases, the nonprofit came up with a new calculation: 10,867.

Eighty percent of the rare diseases are theoretically diagnosable because they have descriptions at the parent or subtype level with three or more phenotypes. The remaining 20% are poorly defined, meaning they include no more than two phenotypes, and as such may not be clinically actionable. More than half of the poorly defined diseases lack a known genetic cause. One-third are non-genetic diseases. 

Some of the difference between RARE-X’s figure and the typical estimates likely stems from its decision to count subtypes of diseases as distinct conditions. So, while one estimate may treat Batten disease as a single condition, the RARE-X analysis separates out the six subtypes of the condition.  

RARE-X argues the question of how many rare diseases exist has real-world implications for whether a condition gets treated. Wendy Erler, vice president of patient experience at Alexion Pharmaceuticals, made the case on a RARE-X podcast.

“Rare diseases often aren't included in standard clinical terminologies. And we know and fundamentally believe better counting of rare diseases will lead to better patient outcomes. Also, as somebody who works for a drug developer, I can state unequivocally, better understanding and counting of rare diseases will lead to more investment in research of these rare diseases, which then can hopefully lead to better treatments,” Erler said.