Phosphoribosyl pyrophosphate synthetase 1 () associated retinal degeneration: an international study.

Introduction: Phosphoribosyl pyrophosphate synthetase 1 () is an X-linked gene critical for nucleotide metabolism. Pathogenic 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 -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 ( = 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 ( = 13), optic atrophy ( = 13), bone spicules ( = 10), and parafoveal outer retinal atrophy = 12) were common findings. Electroretinogram showed delayed and attenuated photopic and scotopic responses ( = 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: -associated retinal degeneration predominantly manifests as a bilateral asymmetric cone and rod dystrophy, commonly associated with hyperopia and optic atrophy.