Clinical Scorecard: Biallelic IDUA Variants Linked to Retinitis Pigmentosa

At a Glance

Key Highlights

• 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.

Guideline-Based Recommendations

Diagnosis

• 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.

Management

• 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.

Monitoring & Follow-up

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

Risks

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

Patient & Prescribing Data

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.

Clinical Best Practices

• 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.

Related Resources & Content

• The American Journal of Human Genetics study described in the article