Genetic Study Links Inherited Blindness to Gene Tied to Rare Metabolic Disorder

Genetic diagnosis can be difficult when a patient’s symptoms do not fit the expected pattern for a known disease gene, particularly when broader systemic features that usually guide diagnosis are absent. Researchers now describe an unexpected link between inherited blindness and a gene typically associated with a rare metabolic disorder.

Greenwood Genetic Center (Greenwood, SC, USA) led an international study identifying changes in the IDUA gene in individuals diagnosed with retinitis pigmentosa. The IDUA gene is typically associated with mucopolysaccharidosis type I, a rare metabolic condition. However, many individuals in the study did not have the severe physical disability, heart problems, or skeletal abnormalities typically associated with mucopolysaccharidosis type I, even at older ages.

The study examined 14 individuals from 12 families with retinitis pigmentosa. Genetic testing showed that all carried changes in both copies of the IDUA gene. Researchers used a functional platform developed at Greenwood Genetic Center to investigate how these IDUA changes affect the body’s ability to produce a critical enzyme.

Laboratory work found that some of the genetic changes allow a very small amount of enzyme activity to remain. Researchers indicated that this residual activity may help explain why these individuals developed retinal disease without the more widespread problems seen in mucopolysaccharidosis type I. 

The findings broaden the known range of conditions associated with IDUA and suggest that the gene should be considered when evaluating patients with inherited retinal disease who lack typical mucopolysaccharidosis type I features.

The study was published in The American Journal of Human Genetics on October 6, 2026. Collaborating institutions included Greenwood Genetic Center, University of Manchester, and more than 20 other centers involved in inherited retinal disease and metabolic disorders. The work also emphasizes the importance of understanding how genetic variants affect the body, rather than identifying variants alone.

“Genetic conditions do not always follow the patterns we expect. Our findings show that changes in the same gene can sometimes affect the retina while leaving other parts of the body largely unaffected. This phenomenon may represent a significant cause of blindness in patients who remain undiagnosed,” said Gavin Arno, Ph.D., associate director of research at Greenwood Genetic Center and the study’s corresponding author.

“This is an excellent example of why genetic diagnosis cannot always stop with identifying a variant in a gene. By combining genetic analysis with laboratory studies, like enzyme levels, we can better understand why a condition may look very different from one person to another,” said Richard Steet, Ph.D., director of research at Greenwood Genetic Center and a study author.

Related Links
Greenwood Genetic Center