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Central Nervous System Manifestations in Cystinosis

A wide range of neurocognitive and mental health complications have been identified in patients with cystinosis. The underlying mechanisms are not completely understood, but may be related to specific structural differences, accumulation of cystine crystals in the brain, and the impact of chronic illness on mental well-being.1-4

Timely recognition of central nervous system (CNS) complications and appropriate interventions and accommodations can improve long-term patient health outcomes, academic and professional success, and psychosocial development.2,5-8

CNS manifestations of cystinosis1-6,9-12
Illustration of the brain
  • Structural/functional brain differences
    • Cerebral atrophy
    • Cerebral calcifications
    • White matter abnormalities
    • Chiari 1 malformation
  • Neurocognitive manifestations
    • Visual spatial/memory/motor impairments
    • Motor processing impairment
    • Executive function impairment
    • Attention deficits
    • Academic deficits

Illustration of the brain

  • Neurologic symptoms/syndromes
    • Idiopathic intracranial hypertension (pseudotumor cerebri)
    • Seizures
    • Stroke and stroke-like episodes
    • Memory concerns
    • Motor incoordination (especially fine motor)
    • Encephalopathy
  • Social, behavioral, and mental health challenges
  • Impaired quality of life
Neurocognitive Challenges in Cystinosis

Neurocognitive differences are among the earliest and most common manifestations of neurologic dysfunction in patients with cystinosis.1 Structural brain differences have been noted in young children with cystinosis, particularly changes in white matter volume and integrity in areas of the brain associated with visual-spatial and visual-memory function.1-3,5

Additional neurocognitive difficulties observed in cystinosis include1,2,5,10-12

  • Impaired gross and fine motor coordination
  • Reduced executive functioning (planning,
    organizing, problem-solving)
  • Delayed processing speed
  • Attention deficits
  • Academic difficulties (especially in math and spelling)
  • Memory deficits

Auditory sensory memory impairments have been observed in children and adolescents with cystinosis; these differences may still be present to a lesser extent in adulthood.11,12

Of those adults diagnosed with cystinosis, up to 40% may experience CNS involvement, including intracranial hypertension, Chiari I malformation, cerebral calcifications and atrophy, and neurocognitive deficits.1,4,13

Overall intelligence, language, and visual-perceptual function typically remain normal in patients with cystinosis.1,2

Mental Health Challenges in Cystinosis

Patients with cystinosis may experience behavioral and psychosocial symptoms. These can include executive functioning and attention deficits, anxiety, depression, and social difficulties.2,3,9,10

Several factors have been shown to negatively affect psychosocial adjustment and quality of life in patients with cystinosis, including2-4,6,9,14

Disease fatigue icon

Disease fatigue

Kidney disease icon

End-stage kidney disease and long-standing dialysis

Job absenteeism icon

School/job absenteeism

Academic difficulties icon

Social/academic/
professional difficulties

Growth failure icon

Growth failure and developmental delays

Photophobia icon

Photophobia

Medication icon

Strict treatment regimen and medication side effects

dollars-icon

Financial burden

Neurologic and Psychosocial Evaluation and Support

The severity and specific areas of cognitive and psychological impairment can vary among individuals. Comprehensive care for patients with cystinosis involves evaluating psychosocial and neurocognitive status regularly and addressing concerns, often with the help of other specialists.6,8

Resources to help patients in the classroom are available.

Depression, anxiety, and psychosocial issues, along with cognitive deficits, can contribute to lower levels of treatment adherence and care engagement. It is crucial to ensure continuity of neurocognitive and mental health support during the transition from pediatric to adult care.2,6,8,9,15

Psychosocial support, including counseling, therapy, and support groups, can help patients and their families cope with the challenges associated with cystinosis. Patient research has revealed that many adults find strength in the cystinosis community via mentoring, information exchange, and shared connections, which help to instill and maintain hope for their future and motivate them to be more active in their disease journey.4,6,7,9,14

Resources to help patients with self-care and self-advocacy are available.

Clinicians can support patients by2,6-8,14

  • Asking about neurocognitive/learning deficits and mental health concerns
  • Referring to specialists (neurologists, neuropsychologists, psychiatrists, therapists, social workers)
  • Encouraging educational/professional accommodations and support services (IEPs or 504 plans)
  • Promoting participation in disease support groups
  • Discussing behavioral interventions and organizational aids

Learn How Cystinosis May
Impact Various Body Systems

Review Extrarenal Manifestations

See How Cystinosis Progresses
at Different Stages

Review Complications of Cystinosis

IEP, individualized education plan.

1. Trauner D. Neurocognitive complications of cystinosis. J Pediatr. 2017;183S:S15-S18. 2. Trauner DA. Neurocognitive complications. J Rare Dis. 2023;2:8. 3. Delgado G, Schatz A, Nichols S, Appelbaum M, Trauner D. Behavioral profiles of children with infantile nephropathic cystinosis. Dev Med Child Neurol. 2005;47(6):403-407. 4. Kasimer RN, Langman CB. Adult complications of nephropathic cystinosis: a systematic review. Pediatr Nephrol. 2021;36(2):223-236. 5. Besouw MTP, Hulstijn-Dirkmaat GM, van der Rijken REA, et al. Neurocognitive functioning in school-aged cystinosis patients. J Inherit Metab Dis. 2010;33(6):787-793. 6. Levtchenko E, Servais A, Hulton SA, et al. Expert guidance on the multidisciplinary management of cystinosis in adolescent and adult patients. Clin Kidney J. 2022;15(9):1675-1684. 7. Bell LE. The transition of a pediatric kidney transplant recipient from childhood to adult care. Clin J Am Soc Nephrol. 2022;17(5):736-738. 8. Fernandez HE, Foster BJ. Long-term care of the pediatric kidney transplant recipient. Clin J Am Soc Nephrol. 2022;17(2):296-304. 9. Beinart N, Hackett RA, Graham CD, Weinman J, Ostermann M. Mood and illness experiences of adults with cystinosis. Ren Fail. 2015;37(5):835-839. 10. Ballantyne AO, Spilkin AM, Trauner DA. Executive function in nephropathic cystinosis. Cogn Behav Neurol. 2013;26(1):14-22. 11. Francisco AA, Foxe JJ, Horsthuis DJ, Molholm S. Impaired auditory sensory memory in cystinosis despite typical sensory processing: a high-density electrical mapping study of the mismatch negativity (MMN). Neuroimage Clin. 2020;25:102170. 12. Francisco AA, Berruti AS, Kaskel FJ, Foxe JJ, Molholm S. Assessing the integrity of auditory processing and sensory memory in adults with cystinosis (CTNS gene mutations). Orphanet J Rare Dis. 2021;16(1):177. 13. Servais A, Saitovitch A, Hummel A, et al. Central nervous system complications in adult cystinosis patients. J Inherit Metab Dis. 2020;43(2):348-356. 14. Cystinosis Research Network. Infantile nephropathic cystinosis: standards of care. Accessed July 28, 2023. https://cystinosis.org/wp-content/uploads/2019/01/CRN_StandardsOfCare_FINAL-1.pdf 15. Raina R, Wang J, Krishnappa V. Structured transition protocol for children with cystinosis. Front Pediatr. 2017;5:191.