Are inherited metabolic disorders more common, and less predictable, than we previously thought?

Large-scale genomic studies are identifying adults with disease-associated variants who have escaped diagnosis, sometimes despite lifelong symptoms. At the same time, expanding genomic newborn screening risks identifying children who may remain well for decades or never develop clinically significant disease at all.

In this episode Dr Nina Gold, Dr Jessica Gold, and Professor Mirjam Langeveld, explore the tension between missed diagnosis and overdiagnosis and ask, when does knowing more genuinely help?

Are Inherited Metabolic Disorders More Common and Less Predictable Than We Thought?

N Gold et al

https://doi.org/10.1002/jimd.70094

Screening for Life: Perspectives From Adult Metabolic Specialists on Newborn Screening for Inherited Metabolic Diseases.

M Langeveld, et al.

https://doi.org/10.1002/jimd.70057

Exclusion-based exome sequencing in critically ill adults 18–40 years old has a 24% diagnostic rate and finds racial disparities in access to genetic testing.

American Journal of Human Genetics

J Gold et al

https://www.cell.com/ajhg/fulltext/S0002-9297(25)00238-1

Long-term Penetrance of Disease Variants in Genes Prioritized for Genomic Newborn Screening.

Gold NB, et al.

https://www.medrxiv.org/content/10.64898/2026.06.10.26355380v1 - pre-print not peer reviewed