Infancy
Adolescence
Adulthood
Adherence Strategies
Symptoms of cystinosis often begin presenting around 6 months of age.1-3 Historically, patients with nephropathic cystinosis were given a lifespan of approximately 10 years.1,2 As a result of improved medical care, including successful renal transplant and early initiation of cystine-depleting therapy (CDT), individuals with cystinosis are living longer, with some living into their 50s and beyond.2,4
*Every undertreated or untreated patient may not experience all the manifestations listed here. Cystinosis progression and presentation may vary among patients. Some preexisting complications may change or become more severe as patients age. Even adequately treated patients may experience these manifestations. This tool includes common symptoms and may not be an exhaustive list of all possible manifestations.
Infancy
Adolescence
Adulthood
Adherence Strategies
By 6-12 months of age, approximately 95% of untreated patients will develop Fanconi syndrome.1-3
Symptoms of Fanconi syndrome include polyuria, polydipsia, electrolyte imbalances, dehydration, rickets, and failure to thrive.1-3,5
Vomiting as a result of Fanconi Syndrome may develop as early as 6 months of age.1,5
Poor appetite, vomiting, and feeding difficulties may contribute to failure to thrive.5,6
Hypophosphatemic rickets may develop by ~1 year of age and contribute to impaired growth, bone deformities, and delayed ambulation.1,2
Infants typically appear normal at birth but may fall below the 3rd percentile for height by the age of 1.1,7
Learn the Importance
of Early
Diagnosis and Treatment
Regular WBC Cystine Level Testing
Can Help Assess Patient
Adherence
GI, gastrointestinal;
WBC, white
blood
cell.
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Neurocognitive complications, including visual-spatial, visual-memory, and attention deficits, may develop in untreated children with cystinosis.9
Many children with cystinosis may experience academic difficulties, particularly in math and spelling, as a result of visual-spatial and visual-memory deficits.9
By 8-12 years of age, 95% of untreated patients develop renal complications.3
Untreated patients may develop ESRD and require RRT or transplant by 10 years of age.5
Many male patients with cystinosis experience late sexual maturation and develop hypogonadism.1,2
Corneal crystals may develop in untreated patients ~16 months of age.1,3,10
By 8-12 years of age, approximately 50% of untreated patients will develop photophobia.1,3
Vision loss will develop in approximately 10%-15% of untreated patients ages 13 years and older.3,10
By 5-10 years of age, approximately 50% of untreated patients will develop hypothyroidism.2,3
Hypothyroidism is among several factors that contribute to impaired growth and delayed puberty in children with cystinosis.1,2
As myopathy progresses, patients may experience swallowing difficulties that worsen as the patient ages.3,11
Swallowing difficulties and feeding problems may contribute to malnutrition and poor growth and may become so severe that some patients require a feeding tube.1,6,11
Myopathy may develop in approximately 20%-75% of untreated patients ages 12 years and older.3,11
Kidneys
Fanconi
syndrome
GI System
Feeding difficulties Poor appetite Vomiting
Bones
Rickets
Failure to thrive
Learn the Importance
of Early
Diagnosis and Treatment
Regular WBC Cystine Level Testing
Can Help Assess Patient
Adherence
ESRD, end stage renal disease; GI,
gastrointestinal; RRT, renal
replacement therapy;
WBC, white
blood
cell.
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Nearly 40% of adults have CNS involvement, including intracranial hypertension, Chiari I malformation, cerebral calcifications and atrophy, and memory deficits.2,9,11,12
Anywhere from 7%-54% of adults with cystinosis may develop diabetes.11
In approximately 50%-80% of young adults, hyperglycemia is exacerbated by prednisone after receiving a kidney transplant.2
Following kidney transplant, cystine continues to accumulate in extrarenal organs.1,13
CDT is often withdrawn for kidney transplant but should be restarted in the early posttransplant period.14
By 21-40 years of age, nearly all patients will develop pulmonary dysfunction.3
Progressive myopathy affects accessory chest muscles, causing pulmonary insufficiency that can be life-threatening.1
Myopathy progresses from the distal muscles of the extremities to more proximal muscles, leading to dysphagia, generalized atrophy, and pulmonary insufficiency.1,11
Up to 85% of adults with cystinosis experience weakness and/or atrophy of the hand and foot muscles.15
Difficulty swallowing is reported by 60% of adults with cystinosis and may lead to feeding problems, aspiration pneumonia, slow eating, and frequent choking episodes.1,15
Infertility is common among men, though the ability to have an erection remains intact.1,2
Cystinosis has not been shown to cause infertility in women, though they may experience a high-risk pregnancy.1,2
Kidneys
Fanconi
syndrome
GI System
Feeding difficulties
Poor appetite
Vomiting
Dysphagia
Bones
Rickets
Failure to thrive
Brain
Neurocognitive
differences
Eyes
Photophobia Vision loss
Thyroid
Hypothyroidism
Muscles
Myopathy
Male Reproductive Organs
Hypogonadism
Learn the Importance
of Early
Diagnosis and Treatment
Regular WBC Cystine Level Testing
Can Help Assess Patient
Adherence
CNS, central nervous system; ESRD, end stage
renal disease; GI,
gastrointestinal;
WBC, white
blood cell.
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Due to the continuous nature of cystine accumulation,
optimal cystine control
requires
strict adherence to treatment.16
Missed and even briefly delayed
doses
of CDT can lead to significant increases in cystine
levels.16 The damage caused by cystine accumulation
may
be irreversible.4,5
Despite the benefits of treatment, strict adherence can be difficult to maintain because of pill burden, dosing frequency, need for lifelong treatment, and adverse effects of CDT.17,18 Patients may have limited understanding of disease progression, challenges during transition to adult care, and psychological impacts of living with a chronic rare disease.17 Adherence to therapy tends to decline in adolescent and adult patients with cystinosis, placing these groups at high risk for poor outcomes.14,17
Simplifying medications and developing individualized treatment plans
Identifying cues or visual reminders, including medication reminders, such as timers, special pill bottles or packs, and phone apps
Enlisting the help of a support person
Implementing and/or reinforcing disease education with the patient’s care team
Encouraging involvement in patient support organizations and/or programs
Identifying patient-specific barriers and implementing practical solutions
Pointing your patient towards cystinosis support resources, such as CystinosisUnited.com
Using the adherence discussion guide and WBC cystine testing to identify nonadherence
Speaking with a representative to identify additional resources for your patient
See How Transition of Care
May
Affect Adherence
Monitor Cystine Levels
to Assess
Treatment Adherence
WBC, white blood cell.
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1. Nesterova G, Gahl W. Nephropathic cystinosis: late complications of a multisystemic disease. Pediatr Nephrol. 2008;23(6):863-878. 2. Cystinosis Research Network. Cystinosis Parent Handbook. Accessed April 2021. https://cystinosis.org/wp-content/uploads/2019/01/CRN_ParentHandbook_FINAL_web-3.pdf 3. Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med. 2002;347(2):111-121. 4. Gahl WA, Balog JZ, Kleta R. Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy.Ann Intern Med. 2007;147(4):242-250. 5. Wilmer MJ, Schoeber JP, van den Heuvel LP, Levtchenko EN. Cystinosis: practical tools for diagnosis and treatment. Pediatr Nephrol. 2011;26(2):205-215. 6. Elenberg E, Norling LL, Kleinman RE, Ingelfinger JR. Feeding problems in cystinosis. Pediatr Nephrol. 1998;12(5):365-370. 7. Gahl WA, Reed GF, Thoene JG, et al. Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med. 1987;316(16):971-977. 8. Jamalpoor A, Othman A, Levtchenko EN, Masereeuw R, Janssen MJ. Molecular mechanisms and treatment options of nephropathic cystinosis. Trends Mol Med. 2021;27(7):673-686. 9. Trauner D. Neurocognitive complications of cystinosis. J Pediatr. 2017;183S:S15-S18. 10. Bishop R. Ocular complications of infantile nephropathic cystinosis. J Pediatr. 2017;183S:S19-S21. 11.M Kasimer RN, Langman CB. Adult complications of nephropathic cystinosis: a systematic review.Pediatr Nephrol. 2021;36(2):223-236. 12. 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. 13. Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E. Cystinosis: a review. Orphanet J Rare Dis. 2016;11:47. 14. Langman CB, Barshop BA, Deschênes G, et al. Controversies and research agenda in nephropathic cystinosis: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int. 2016;89(6):1192-1203. 15. Sadjadi R, Sullivan S, Grant N, et al. Clinical myopathy in patients with nephropathic cystinosis. Muscle Nerve. 2020;61(1):74-80. 16. Levtchenko EN, van Dael CM, de Graaf-Hess AC, et al. Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis.Pediatr Nephrol. 2006;21(1):110-113. 17. Ariceta G, Camacho JA, Fernández-Obispo M, et al. Cystinosis in adult and adolescent patients: recommendations for the comprehensive care of cystinosis. Nefrología. 2015;35(3):304-321. 18. Varnell CD Jr, Rich KL, Nichols M, et al. Assessing barriers to adherence in routine clinical care for pediatric kidney transplant patients. Pediatr Transplant. 2017;21(7):10.1111/petr.13027. 19. Cheung CY, Chan KM, Tang G, Cheung A, Chak WL. Immunosuppressive medication adherence in kidney transplant recipients during the COVID-19 pandemic: a cross-sectional study in Hong Kong. Transplant Proc. 2021;53(8):2447-2450. 20. Loghman-Adham M. Medication noncompliance in patients with chronic disease: issues in dialysis and renal transplantation. Am J Manag Care. 2003;9(2):155-171.
