Genetic Link Explains Inherited Blindness

Study identifies gene variants associated with retinal degeneration in patients without the systemic symptoms of a rare metabolic disorder

Category	Detail
Condition	Retinitis pigmentosa in people with variants affecting both copies of IDUA and markedly reduced α-L-iduronidase activity
Key Mechanisms	Variants affecting both copies of IDUA were associated with reduced α-L-iduronidase activity; long-read RNA sequencing identified abnormal splicing for a recurrent variant.
Target Population	People with retinitis pigmentosa and biallelic IDUA variants
Care Setting	Inherited retinal disease genetic evaluation, with biochemical investigations and referral for metabolic assessment as described by the authors

The study examined 14 people from 12 families with retinitis pigmentosa and variants affecting both copies of IDUA.
Seven participants had no systemic features consistent with MPS I despite comprehensive clinical evaluation.
Testing in nine individuals found detectable but greatly reduced α-L-iduronidase activity; some variants retained approximately 0.5% to 1.5% of normal activity.
Long-read RNA sequencing revealed abnormal splicing of a recurrent IDUA variant, despite conventional protein-based testing suggesting little functional impact.
The authors recommend including IDUA and other MPS-associated genes in inherited retinal disease testing panels.

The authors recommend including IDUA and other MPS-associated genes in inherited retinal disease testing panels.
The authors describe combining genomic sequencing, enzyme activity measurements, and functional studies to interpret potentially uncertain variants.

The authors state that follow-up biochemical investigations, including leukocyte enzyme activity and urinary glycosaminoglycan analysis, may help establish a diagnosis and guide referral for metabolic assessment when variants affecting both IDUA copies are identified.

The article notes possible implications for clinical surveillance but does not specify a surveillance schedule.

The study was limited by its small cohort and incomplete longitudinal follow-up.

Fourteen individuals from 12 families with retinitis pigmentosa and biallelic IDUA variants; seven had no systemic features consistent with MPS I.

The article reports diagnostic evaluation and referral considerations, not treatment regimens or prescribing data.

The authors describe leukocyte α-L-iduronidase activity testing and urinary glycosaminoglycan analysis as follow-up investigations for biallelic IDUA findings.
The study used RNA analysis to investigate abnormal splicing of a recurrent IDUA variant that appeared to have little impact in conventional protein-based testing.
The authors state that follow-up investigations may guide referral for metabolic assessment.