Genomic Testing Program Improves Diagnosis of Congenital Hyperinsulinism

Differentiating diffuse from focal disease is crucial because focal cases may be surgically curable, yet access to timely genomic testing remains uneven worldwide. Aligning therapy with the underlying genetic cause can also inform surveillance for syndromic presentations. New findings demonstrate a coordinated program that expands rapid genomic testing and documents outcomes across more than 1,100 affected families.

The Open Hyperinsulinism Genes Project is a partnership between the University of Exeter, Royal Devon University Healthcare NHS Foundation Trust, and U.S.-based Congenital Hyperinsulinism International to deliver comprehensive, rapid genomic testing for congenital hyperinsulinism. The program is designed to improve equitable access to genomic medicine for families who cannot obtain testing in their home countries. Exeter provides testing and connects participating families with research opportunities that would otherwise be unavailable to them.

Through genetic analysis, the initiative confirms whether insulin excess arises from the entire pancreas (diffuse disease) or from a localized pancreatic region (focal disease). That distinction guides treatment, as focal disease can be cured by resecting the over-secreting cells, and early surgery reduces the risk of hypoglycemia-related brain injury. Testing also identifies syndromic forms of hyperinsulinism to enable appropriate clinical monitoring.

A correspondence article in Nature Health describes outcomes since the project’s 2018 launch, including funded rapid testing for more than 1,100 families across 63 countries on six continents. The Exeter team delivered a molecular diagnosis for 593 children (52%). Among diagnosed cases, 438 were consistent with diffuse disease and 155 were predicted to have focal disease; a syndromic form of hyperinsulinism was identified in 29 infants.

The collaboration reports that enrolling families from populations underrepresented in genomic studies increases genetic diversity and strengthens the global relevance of resulting discoveries. Project-led research has already deepened understanding of the genetic basis of congenital hyperinsulinism and advanced knowledge of insulin secretion biology and gene regulation. 

“In Exeter, we are committed to ensuring that every child born with congenital hyperinsulinism, wherever they are in the world, can benefit from rapid, state-of-the-art genetic testing, something that has not previously been possible. This project combines Exeter's world-leading genetics expertise with knowledge of the condition ... from Congenital Hyperinsulinism International,” said Sarah Flanagan, professor at the University of Exeter Medical School and lead of the research program.

“This alliance is unlocking access to rapid genomic testing for families across the world, giving children the best chance in life and expanding research to be more inclusive. We believe this model should be expanded to other rare diseases,” said Jayne Houghton, lead clinical scientist for the project at the Royal Devon University Healthcare NHS Foundation Trust.

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