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

Xue Zhong Liu, Dinghua Xie, Hui Jun Yuan, Arjan P.M. De Brouwer, John Christodoulou, Denise Yan

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)23-28
Number of pages6
JournalInternational Journal of Audiology
Issue number1
StatePublished - Jan 2013


  • Genetic deafness
  • Hearing impairment
  • Mutation
  • Phenotypic variation
  • PRPS1
  • Sex-linked

ASJC Scopus subject areas

  • Speech and Hearing
  • Language and Linguistics
  • Linguistics and Language


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