What this study looked at
Mucopolysaccharidosis type I (MPS I) is a rare inherited disorder caused by changes in the IDUA gene. Drawing on an extensive series of 538 patients from an international registry, this study examined how a person's specific genetic variants relate to how severe their disease is.
Key takeaways
- Around two-thirds (67.6%) of patients with severe MPS I carried two IDUA variants predicted to leave the gene completely non-functional.
- Having two such severe variants — whether identical or different — always resulted in severe disease.
- None of the 158 patients with the milder, attenuated form had two severely disruptive variants; almost all (95.6%) carried at least one missense variant, with the rest having a splice site, intronic or small in-frame change.
Why it matters
Linking particular genetic changes to disease severity can help clinicians and families anticipate how MPS I is likely to progress and inform decisions about care.
