title: 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.
  
  
  METHODS
  A literature search of peer-reviewed, published journal articles was conducted in online bibliographic databases.
  
  
  METHODS
  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.
authors.affiliation: Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA. xliu@med.Miami.edu
authors.forename: Xue Zhong
authors.initials: XZ
authors.lastname: Liu
authors.forename: Dinghua
authors.initials: D
authors.lastname: Xie
authors.forename: Hui Jun
authors.initials: HJ
authors.lastname: Yuan
authors.forename: Arjan P M
authors.initials: AP
authors.lastname: de Brouwer
authors.forename: John
authors.initials: J
authors.lastname: Christodoulou
authors.forename: Denise
authors.initials: D
authors.lastname: Yan
mesh_terms: D019587:Dietary Supplements; D005260:Female; D020022:Genetic Predisposition to Disease; D006309:Hearing / Q000235:genetics*; D034381:Hearing Loss / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D040941:Heredity; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D012268:Ribose-Phosphate Pyrophosphokinase / Q000235:genetics*; D012436:S-Adenosylmethionine / Q000627:therapeutic use; D012720:Severity of Illness Index; D012737:Sex Factors
chemical_list: D012436:S-Adenosylmethionine; C510474:PRPS1 protein, human; D012268:Ribose-Phosphate Pyrophosphokinase