Hearing loss and PRPS1 mutations: Wide spectrum of phenotypes and potential therapy

Abstract

Objective: The purpose of this review was to evaluate the current literature on phosphoribosylpyrophosphate synthetase 1 (PRPS1)-related diseases and their consequences on hearing function. Design: A literature search of peer-reviewed, published journal articles was conducted in online bibliographic databases. Study sample: Three databases for medical research were included in this review. Results: Mutations in PRPS1 are associated with a spectrum of non-syndromic to syndromic hearing loss. Hearing loss in male patients with PRPS1 mutations is bilateral, moderate to profound, and can be prelingual or postlingual, progressive or non-progressive. Audiogram shapes associated with PRPS1 deafness are usually residual and flat. Female carriers can have unilateral or bilateral hearing impairment. Gain of function mutations in PRPS1 cause a superactivity of the PRS-I protein whereas the loss-of-function mutations result in X-linked nonsyndromic sensorineural deafness type 2 (DFN2), or in syndromic deafness including Arts syndrome and X-linked Charcot-Marie-Tooth disease-5 (CMTX5). Conclusions: Lower residual activity in PRS-I leads to a more severe clinical manifestation. Clinical and molecular findings suggest that the four PRPS1 disorders discovered to date belong to the same disease spectrum. Dietary supplementation with S-adenosylmethionine (SAM) appeared to alleviate the symptoms of Arts syndrome patients, suggesting that SAM could compensate for PRS-I deficiency.

Key Words::

• PRPS1
• sex-linked
• mutation
• genetic deafness
• phenotypic variation
• hearing impairment

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by NIH grants NIH DC05575 and DC012546, Hurong Research Scholar Award, and Oversea Chinese Research Scholar Award from the NNSF of China to XZL.