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Published on: December 12, 2014
Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) associated retinal degeneration: an international study
Ogul E Uner1, Radwa Elsharawi1, Margaret Reynolds2
1Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.
Insights
Pathogenic variants in the Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) gene cause retinal degeneration, often presenting as asymmetric cone and rod dystrophy. This condition is frequently linked with hyperopia and optic atrophy in affected individuals.
Area of Science:
- Genetics
- Ophthalmology
- Neurology
Background:
- Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is an X-linked gene essential for nucleotide metabolism.
- Pathogenic PRPS1 variants are associated with Arts syndrome, Charcot-Marie-Tooth type 5 (CMTX5), and sensorineural hearing loss (SNHL), potentially including retinal dystrophy.
Purpose of the Study:
- To describe the clinical characteristics of PRPS1-associated retinal degeneration.
- To investigate the phenotypic spectrum of PRPS1-related ocular disease across multiple centers.
Main Methods:
- A multicenter retrospective clinical case series.
- Analysis of data from 15 patients across 12 pedigrees with PRPS1-associated retinal degeneration.
Main Results:
- PRPS1-associated retinal degeneration predominantly affects females (73.3%) with a mean age of ocular onset at 8.5 years.
- Common findings include macular and optic atrophy, bone spicules, parafoveal outer retinal atrophy, hyperopia, and asymmetric visual acuity.
- Electroretinograms reveal delayed and attenuated photopic and scotopic responses, indicating significant retinal dysfunction.
Conclusions:
- PRPS1-associated retinal degeneration typically presents as a bilateral, asymmetric cone and rod dystrophy.
- The condition is commonly associated with hyperopia and optic atrophy, highlighting the ocular manifestations of PRPS1 gene variants.
Introduction:
Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is an X-linked gene critical for nucleotide metabolism. Pathogenic PRPS1 variants cause three overlapping phenotypes: Arts syndrome (severe neurological disease), Charcot-Marie-Tooth type 5 [CMTX5] (peripheral neuropathy), and non-syndromic sensorineural hearing loss (SNHL). Each may be associated with retinal dystrophy. Multicenter phenotypic studies are limited.
Methods:
A multicenter retrospective clinical case series of 15 patients from 12 pedigrees with PRPS1-associated retinal degeneration is presented.
Results:
Of 15 patients, 11 (73.3%) were female. Mean age of ocular disease onset was 8.5 years (range, 0.5-35 years). Many were diagnosed with Leber congenital amaurosis prior to genetic testing (n = 5). Five patients had clinical diagnoses of CMTX5 and Arts syndrome, two had isolated ocular disease, and one was asymptomatic. Mean initial VA (LogMAR) was 0.74, 0.74, 0.83, and 0.85 for isolated ocular disease, CMTX5, Arts, and SNHL, respectively. Ten patients were hyperopic and eight had asymmetric VA. Macular atrophy (n = 13), optic atrophy (n = 13), bone spicules (n = 10), and parafoveal outer retinal atrophy (n = 12) were common findings. Electroretinogram showed delayed and attenuated photopic and scotopic responses (n = 10). Median follow-up of 2.9 years (range, 1.5-11.6 years) in six patients showed retinal disease progression in two patients.
Discussion:
PRPS1-associated retinal degeneration predominantly manifests as a bilateral asymmetric cone and rod dystrophy, commonly associated with hyperopia and optic atrophy.
