Accelerating Rare Disease Diagnosis With Mondo

Coryssa Barnes, of Henderson, N.C., welcomed her first child, Ezra, successful 2020. At 4 months old, he was incapable to beryllium without support. As clip went on, he grounded to scope different developmental milestones, prompting his worried parents to consult respective aesculapian experts.

"Something was not, you know, not clicking really it's expected to," said Barnes done tears. "The doctors each came backmost to america to opportunity that they didn't person a diagnosis. We had a operation of worry and nerves because you don't want thing to beryllium incorrect pinch your kid."

Following a twelvemonth of unknowns and anxiety, Ezra was officially diagnosed astatine UNC Health. He has a uncommon neurodevelopmental upset known arsenic CTNNB1 syndrome that was first described successful 2012. It results from alterations successful nan CTNNB1 cistron and is distinguished by developmental delays, intelligence disability, and reside impairment.

Ezra was 1 of nan first patients successful nan UNC Health strategy to beryllium diagnosed pinch CTNNB1. His family is 1 of galore who person had to navigate nan agelong and analyzable process of receiving a uncommon illness diagnosis, often referred to arsenic nan "diagnostic odyssey."

Melissa Haendel, PhD, a distinguished professor of genetics astatine nan UNC School of Medicine, and collaborators astatine nan Monarch Initiative are helping to amended nan diagnostic odyssey for uncommon illness patients. In business pinch uncommon illness master organizations, Monarch has coordinated nan Mondo Disease Ontology (Mondo), which intends to harmonize fragmented and difficult to place uncommon illness knowledge.

"Physicians are challenged to diagnose patients pinch very uncommon diseases, alleged 'zebras' because they are truthful rare," said Haendel, who is an master connected precision wellness and translational informatics. "This makes moving nan correct trial and identifying nan champion curen for their patients particularly difficult. Mondo expedites this process by gathering fragmented uncommon illness knowledge from astir nan world and associating it pinch 1 elemental diagnostic codification that will thief patients get connected nan correct way earlier."

As portion of its February 2026 package update, Epic-the nation's astir wide utilized physics wellness grounds (EHR) system-now allows wellness systems that usage IMO Core to besides usage Mondo illness codes straight successful Epic EHRs.

IMO Health's objective terminology level powers objective archiving crossed astir healthcare organizations, making nan modular an action disposable crossed North Carolina, nan United States, and nan world. Mondo illness codes will beryllium disposable crossed UNC Health's 20 hospitals and much than 900 clinics wrong nan year.

The situation for uncommon illness patients and their providers

Rare diseases are challenging to diagnose owed to scattered and inconsistent accusation crossed aesculapian databases. Without speedy and easy entree to uncommon illness knowledge, physicians whitethorn springiness delayed aliases incorrect diagnoses. This is particularly a interest for those successful agrarian aliases superior attraction settings who are not experts successful uncommon and familial disease.

Oftentimes, patients pinch a uncommon illness ne'er get past their superior attraction physician. We tin thief build objective determination support devices overmuch further upstream. Together pinch UNC Health, we purpose to thief superior attraction physicians place symptoms, tally tests, and get their patients referred to a master arsenic soon arsenic possible."

Melissa Haendel, PhD, a distinguished professor of genetics, UNC School of Medicine

Medical databases crossed nan world person different definitions and classifications for conditions, starring to inconsistent terminology for uncommon diseases. For example, "CTNNB1 syndrome" mightiness beryllium called "CTNNB1-related intelligence disability" successful 1 database and "severe intelligence disability-progressive spastic diplegia syndrome" successful another, making it moreover much difficult to track, diagnose, and investigation these conditions.

"It's for illustration a large hairball that we person to disentangle," said Haendel. "Everyone was chipping distant astatine small pieces of documenting diseases crossed academia and successful medicine. We wanted to make it imaginable to person a azygous coding strategy successful nan EHR for uncommon diseases to merge fragmented communities of resources."

How Mondo facilitates much accelerated diagnosis

Mondo useful by consolidating uncommon illness knowledge and terminology from aggregate master aesculapian databases successful an AI-friendly way, including ClinGen, Orphanet, International Classification of Diseases (ICD), and OMIM, into 1 Mondo "code."

Upon diagnosis, nan codification is added to nan patient's physics wellness grounds to thief different physicians and researchers define, track, salary for, and investigation uncommon diseases. Of nan millions of uncommon illness patients globally, astir do not person an ICD codification aliases diagnosis. Mondo introduces astir 5,000 caller uncommon illness codes and updates much than 25,000 related illness codes successful nan Epic system.

"I've ever said that having a uncommon illness test is for illustration yet having a name," said Haendel. "And if nan wellness strategy can't count uncommon diseases done coding, past uncommon illness patients won't count. And they merit to beryllium heard and seen, nary matter really uncommon nan condition."

Securing a caller ICD codification is an arduous process that takes years, demanding important effort, and organization coordination of diligent groups, which do not beryllium for each uncommon disease. Given nan dense caregiving responsibilities specified groups already face, a systematic attack for illustration Mondo is captious for streaming their care.

With thief from diligent defense groups CTNNB1 Connect and Cure and nan Consortium for Outcome Measures and Biomarkers for Neurodevelopmental Disorders (COMBINEDBrain), CTNNB1 syndrome was yet "given an EHR name" successful nan International Classification of Diseases, Tenth Revision, Clinical Modification, aliases nan ICD-10-CM.

"Having nan correct test is everything," said Barnes. "If we didn't push for a diagnosis, we would person missed retired connected an opportunity to cognize much astir his syndrome and nan champion steps to return successful position of resources, appointments, decisions, specialties, and medications."

The Barnes family's acquisition is acold from unique. Across nan uncommon illness community, patients walk years cycling done nan aesculapian strategy without a test aliases an EHR code. This leaves physicians and patients successful a silo, limiting their expertise to find nan treatments and organization they need. Mondo intends to alteration this narrative.

Mondo will bring nan clarity of uncommon illness test overmuch sooner for thousands of uncommon illness patients. In collaboration pinch IMO Health, Epic EHR systems now person nan expertise to usage nan Mondo codification for conditions for illustration CTNNB1 syndrome. In Ezra's case, nan Mondo code, MONDO:0014035, will drawstring together his wellness information and streamline his attraction for years to come.

A test brings organization and support

Now 5 years going connected six, Ezra, who is non-verbal and requires mobility devices, continues to flourish successful his ain unsocial way.

"It's really conscionable inspiring to watch this small kid usage his ain augmentative and replacement connection (AAC) device, erstwhile he wants to," said Barnes pinch a chuckle. "He's a very agleam boy and he tin place shapes and colors and numbers now."

After uncovering a test for Ezra, Barnes recovered a location wrong nan uncommon illness online community. She first built rapport pinch families connected a backstage CTNNB1 Facebook page, wherever she learned much astir investigation news, master recommendations, family advice, and different perspectives.

Barnes would for illustration different families to enactment affirmative and to ever retrieve that location are different families going done nan aforesaid aliases akin uncommon illness experience.

"I really deliberation it's important for group to find their people, particularly successful nan uncommon illness community," said Barnes. "It is specified a different world and it's difficult to subordinate to group who don't get it."

Thanks to Mondo, different children and adults will beryllium fixed an EHR name, giving them speedy entree to treatments, research, and a organization of others who understand what they're going through.

The Mondo Disease Ontology was chiefly funded by nan National Institute of Health Office of Research Infrastructure Program and nan National Human Genome Research Institute assistance numbers 5R24OD011883 and 5RM1HG010860. The Monarch Initiative is an world statement led by UNC, Lawrence Berkeley National Laboratory, nan European Bioinformatics Institute, and Queen Mary University of London.