August 15, 2025

Retinal Degeneration Diagnosed at 12 and 13 Months and Sensorineural Hearing Loss in Two Unrelated Female Infants With PRS Deficiency.

Key Points

Retinal degeneration was diagnosed at 12 and 13 months in two female infants with PRS deficiency, highlighting early ocular manifestations.
Both patients presented with a pathogenic PRPS1 variant, contributing to the understanding of phenotypic diversity associated with PRS deficiency.
This observational analysis of two unrelated cases shows milder yet significant symptoms in females, contrasting with usual male presentations.
The findings suggest that current knowledge of PRS deficiency's clinical spectrum needs to be updated and expanded.

Abstract

Phosphoribosyl pyrophosphate synthetase (PRS) deficiency, an X-linked condition caused by loss-of-function variants in PRPS1, manifests as a phenotypic continuum encompassing three previously distinct disorders: Arts syndrome, Charcot-Marie-Tooth neuropathy X type 5 (CMTX5), and X-linked nonsyndromic sensorineural hearing loss (DFNX1). Males are typically more severely affected, while females with the same variant often present with milder forms. We report two unrelated female patients with progressive sensorineural hearing loss and very early-onset retinal degeneration, at 12 and 13 months, respectively, and a pathogenic PRPS1 c.640C>T p.(Arg214Trp) variant. Notably, these cases show retinal involvement earlier than previously reported, expanding the clinical spectrum of PRS deficiency. This report contributes to the growing understanding of the phenotypic variability and complexity of this condition, particularly regarding early ocular manifestations.

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