PRPS1 loss-of-function variants, from isolated hearing loss to severe congenital encephalopathy: New cases and literature review

Eur J Med Genet. 2020 Nov;63(11):104033. doi: 10.1016/j.ejmg.2020.104033. Epub 2020 Aug 8.


We describe two sporadic and two familial cases with loss-of-function variants in PRPS1, which is located on the X chromosome and encodes phosphoribosyl pyrophosphate synthetase 1 (PRS-1). We illustrate the clinical variability associated with decreased PRS-1 activity, ranging from mild isolated hearing loss to severe encephalopathy. One of the variants we identified has already been reported with a phenotype similar to our patient's, whereas the other three were unknown. The clinical and biochemical information we provide will hopefully contribute to gain insight into the correlation between genotype and phenotype of this rare condition, both in females and in males. Moreover, our observation of a new family in which hemizygous males display hearing loss without any neurological or ophthalmological symptoms prompts us to suggest analysing PRPS1 in cases of isolated hearing loss. Eventually, PRPS1 variants should be considered as a differential diagnosis of mitochondrial disorders.

Keywords: Arts syndrome; Deafness; Hearing loss; Intellectual deficiency; PRPS1.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Ataxia / genetics*
  • Ataxia / pathology
  • Child
  • Deaf-Blind Disorders / genetics*
  • Deaf-Blind Disorders / pathology
  • Female
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / pathology
  • Humans
  • Infant
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Loss of Function Mutation*
  • Male
  • Pedigree
  • Phenotype*
  • Ribose-Phosphate Pyrophosphokinase / genetics*


  • PRPS1 protein, human
  • Ribose-Phosphate Pyrophosphokinase

Supplementary concepts

  • Arts syndrome