Event-related potential (ERP) evidence for visual processing differences in children and adults with cystinosis (CTNS gene mutations)

Orphanet J Rare Dis. 2023 Dec 12;18(1):389. doi: 10.1186/s13023-023-02985-y.


Background: Cystinosis, a rare lysosomal storage disease caused by mutations in the CTNS gene, is characterized by cystine crystallization and accumulation within multiple tissues, including kidney and brain. Its impact on neural function appears mild relative to its effects on other organs during early disease, but since therapeutic advances have led to substantially increased life expectancy, neurological implications are of increasing interest, necessitating deeper understanding of the impact of cystinosis on neurocognitive function. Behavioral difficulties have been reported in cystinosis in the visual domain. Very little is known, however, about how the brains of people living with cystinosis process visual information. This is especially interesting given that cystine accumulation in the cornea and posterior ocular structures is a hallmark of cystinosis.

Methods: Here, high-density scalp electrophysiology was recorded to visual stimuli (during a Go/No-Go task) to investigate visual processing in individuals with cystinosis, compared to age-matched controls. Analyses focused on early stages of cortical visual processing.

Results: The groups differed in their initial cortical response, with individuals with cystinosis exhibiting a significantly larger visual evoked potential (VEP) in the 130-150 ms time window. The groups also differed in the associations between neural responses and verbal abilities: While controls with higher IQ scores presented larger neural responses, that relationship was not observed in cystinosis.

Conclusions: The enlarged VEP in cystinosis could be the result of cortical hyperexcitability and/or differences in attentional engagement and explain, at least partially, the visual and visual-spatial difficulties described in this population.

Keywords: Copy number variation; EEG; Lysosomal storage disorder; P1; Visual evoked potential.

MeSH terms

  • Adult
  • Amino Acid Transport Systems, Neutral* / genetics
  • Amino Acid Transport Systems, Neutral* / therapeutic use
  • Child
  • Cystine / genetics
  • Cystine / metabolism
  • Cystine / therapeutic use
  • Cystinosis* / drug therapy
  • Cystinosis* / genetics
  • Evoked Potentials, Visual
  • Eye Diseases*
  • Humans
  • Mutation / genetics
  • Visual Perception


  • Cystine
  • Amino Acid Transport Systems, Neutral
  • CTNS protein, human