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

Int J Audiol. 2013 Jan;52(1):23-8. doi: 10.3109/14992027.2012.736032. Epub 2012 Nov 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Dietary Supplements
  • Female
  • Genetic Predisposition to Disease
  • Hearing / genetics*
  • Hearing Loss / diagnosis
  • Hearing Loss / drug therapy
  • Hearing Loss / enzymology
  • Hearing Loss / genetics*
  • Hearing Loss / physiopathology
  • Heredity
  • Humans
  • Male
  • Mutation*
  • Phenotype
  • Ribose-Phosphate Pyrophosphokinase / genetics*
  • S-Adenosylmethionine / therapeutic use
  • Severity of Illness Index
  • Sex Factors


  • S-Adenosylmethionine
  • PRPS1 protein, human
  • Ribose-Phosphate Pyrophosphokinase