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Arts Syndrome

Arts syndrome is a rare and severe neurological disorder that can cause various problems in males, including sensorineural hearing loss (hearing loss due to issues with the inner ear and its nerves), optic nerve atrophy (a cause of vision loss), intellectual disability, difficulties with body movement including ataxia (lack of coordination) and hypotonia (weak muscle tone), peripheral neuropathy (loss of sensation in the limbs), and recurrent respiratory infections due to inability to clear the lungs and weakness of the immune system (the body’s system for fighting infections)1.  Arts syndrome is caused by mutations in the PRPS1 gene which is located on the X chromosome. PRPS1 is necessary for creating the building blocks for DNA and molecules like ATP which cells use as a source of energy. So, because they have a defective PRPS1 gene, patients with Arts syndrome will have poor function in cells of the body that use a lot of energy and work hard, including the cells of the nervous system and the immune system. Males with Arts syndrome historically have severe disease beginning early in life (often at birth) and often do not live past childhood due to complications from infections1. Arts syndrome is the most severe of several diseases caused by mutations in the PRPS1 gene2.

 

Females with Arts Syndrome

Female carriers of Arts syndrome, i.e. females who have a highly pathogenic (harmful) PRPS1 mutation on one of their two X chromosomes (heterozygotes), are usually asymptomatic. However, some of these females have been reported to experience symptoms themselves which are milder than males with Arts syndrome. Specifically, some female carriers have been reported to experience hearing loss, vision loss from optic nerve atrophy and retinitis pigmentosa, peripheral neuropathy (weakness and loss of sensation in limbs) and ataxia (poor coordination, often causing difficulty walking)2-5. In most reported cases of symptomatic females, the onset of their symptoms began in late childhood or adulthood and the disease progressed slowly. However, this seems to be variable, as two unrelated females have been reported to have very early-onset retinal degeneration (a cause of vision loss) and early hearing loss diagnosed at just 12–13 months of age6.

The development of disease features in female carriers of Arts syndrome is thought to be due to skewed X-inactivation (where a majority of cells express the X chromosome with the “bad” copy of PRPS1), though this has not been proven as the cause in every case. One family with three symptomatic females was reported in 2014, and it was noted that there was significant variability in the features and severity of disease experienced by each family member despite having the same genetic variant in PRPS13. In that family, one of the females had a severe, “full” phenotype of the disease that was comparable to males with Arts syndrome, and it was found that she had complete skewing of her X chromosomes, with total absence of the normal copy of PRPS1 in her blood cells. This rare and significant skewing is thought to explain her severe disease that is highly unusual amongst females.

In general, having one healthy copy of PRPS1 is able to protect females from severe symptoms, and those symptoms that do develop are generally mild and are not known to shorten life length. That said, the risk of female carriers developing symptoms exists, so routine assessments of hearing and vision are warranted for these patients, as are neurologic evaluations if changes in gait (walking) or brain function arise. Unfortunately, the percentage of female carriers of PRPS1 variants who develop symptoms of disease is not known.

This page was last updated in August, 2026. Please note that research into this condition is limited, with very few cases reported. As a result, information may not be accurate to the current day or widely applicable. Decisions regarding your own health should be made in consultation with your medical provider.

  1. Arts syndrome: MedlinePlus Genetics. Accessed August 11, 2026. https://medlineplus.gov/genetics/condition/arts-syndrome/ 
  2. de Brouwer APM, van Bokhoven H, Nabuurs SB, Arts WF, Christodoulou J, Duley J. PRPS1 Mutations: Four Distinct Syndromes and Potential Treatment. Am J Hum Genet. 2010;86(4):506-518. doi:10.1016/j.ajhg.2010.02.024 
  3. Almoguera B, He S, Corton M, et al. Expanding the phenotype of PRPS1 syndromes in females: neuropathy, hearing loss and retinopathy. Orphanet J Rare Dis. 2014;9:190. doi:10.1186/s13023-014-0190-9 
  4. Rezende Filho FM, Palma MM, Pedroso JL, Barsottini OG, Sallum JM. PRPS1 Gene Mutation Causes Complex X-Linked Adult-Onset Cerebellar Ataxia in Women. Neurol Genet. 2021;7(2):e563. doi:10.1212/NXG.0000000000000563 
  5. Missense variants in the X‐linked gene PRPS1 cause retinal degeneration in females – Fiorentino – 2018 – Human Mutation – Wiley Online Library. Accessed August 11, 2026. https://onlinelibrary-wiley-com.ezproxy.cul.columbia.edu/doi/10.1002/humu.23349 
  6. Zocche D, Moosajee M, Kulkarni AM, Henderson RH, Clement E, Ibitoye R. Retinal Degeneration Diagnosed at 12 and 13 Months and Sensorineural Hearing Loss in Two Unrelated Female Infants With PRS Deficiency. Am J Med Genet A. 2026;200(1):192-198. doi:10.1002/ajmg.a.64227