Cystinosis

Cystinosis
Other names	Cystine storage disease, [1] Abderhalden–Lignac–Kaufmann disease, [2] Abderhalden–Kaufmann–Lignac syndrome
Chemical structure of cystine formed from L-cysteine (under biological conditions)
Specialty	Endocrinology

Cystinosis is a lysosomal storage disease characterized by the abnormal accumulation of free cystine, the oxidized dimer of the amino acid cysteine in lysosomes, eventually leading to intracellular crystal formation throughout the body, e.g. in kidneys. ^[3]

It is genetically inheritable in the autosomal recessive fashion via CTNS (AR) gene. ^[4] It characterized by systemic accumulation of the amino acid cystine within lysosomes, proximal tubulopathy and by progressive chronic kidney disease. If untreated, it leads to progressive cellular dysfunction and multiorgan involvement. The disease most commonly presents in infancy with renal Fanconi syndrome and, without treatment, progresses to end-stage kidney disease (ESKD) in childhood. Extra-renal manifestations affecting the eyes, thyroid, muscle, pancreas, and central nervous system may develop later in life. Early diagnosis and lifelong cystine-depleting therapy improve growth, delay progression to ESKD, and reduce many systemic complications. ^{[5] [6] [7]} Nevertheless, despite treatment, the mean age at death for individuals born between 1985 and 1999 has been 29 years. ^[8]

Cystinosis is the most common cause of Fanconi syndrome in the pediatric age group. Fanconi syndrome occurs when the function of cells in renal tubules is impaired, leading to abnormal amounts of carbohydrates and amino acids in the urine, excessive urination, and low blood levels of potassium and phosphates. ^[9]

Cystinosis was the first documented genetic disease belonging to the group of lysosomal storage disease disorders. ^[10] Cystinosis is caused by mutations in the CTNS gene that codes for cystinosin, the lysosomal membrane-specific transporter for cystine. Intracellular metabolism of cystine, as it happens with all amino acids, requires its transport across the cell membrane. After degradation of endocytosed protein to cystine within lysosomes, it is normally transported to the cytosol. But if there is a defect in the carrier protein, cystine is accumulated in lysosomes. As cystine is highly insoluble, when its concentration in tissue lysosomes increases, its solubility is immediately exceeded and crystalline precipitates are formed in almost all organs and tissues. ^[11]

However, the progression of the disease is not related to the presence of crystals in target tissues. Although tissue damage might depend on cystine accumulation, the mechanisms of tissue damage are not fully understood. Increased intracellular cystine profoundly disturbs cellular oxidative metabolism and glutathione status, ^[12] leading to altered mitochondrial energy metabolism, autophagy, and apoptosis. ^[13]

Cystinosis is usually treated with cysteamine, which is prescribed to decrease intralysosomal cystine accumulation. ^[14] However, the discovery of new pathogenic mechanisms and the development of an animal model of the disease may open possibilities for the development of new treatment modalities to improve long-term prognosis. ^[10]

Classification

• Infantile (classic) nephropathic cystinosis Online Mendelian Inheritance in Man (OMIM): 219800  : the most common and severe form, presenting within the first year of life with Fanconi syndrome and rapid progression to renal failure. ^[15]

• Juvenile (intermediate) cystinosis Online Mendelian Inheritance in Man (OMIM): 219900  : later onset and slower progression. ^[16]

• Ocular (non-nephropathic or adult) cystinosis Online Mendelian Inheritance in Man (OMIM): 219750: primarily limited to the eyes with minimal or no renal involvement. ^[17]

Symptoms and signs

There are three distinct types of cystinosis each with slightly different symptoms: nephropathic cystinosis, intermediate cystinosis, and non-nephropathic or ocular cystinosis. Infants affected by nephropathic cystinosis initially exhibit poor growth and particular kidney problems (sometimes called renal Fanconi syndrome). The kidney problems lead to the loss of important minerals, salts, fluids, and other nutrients. The loss of nutrients not only impairs growth, but may result in soft, bowed bones (hypophosphatemic rickets), especially in the legs. The nutrient imbalances in the body lead to increased urination, thirst, dehydration, and abnormally acidic blood (acidosis). ^{[9] [1]}

Slit-lamp photographs of three-year-old patient with nephropathic cystinosis before (left) and after (right) cysteamine eyedrop therapy. The drops dissolve the crystals in the cornea.

Presentation in the first 6–12 months with poor growth, polyuria, polydipsia, dehydration, and rickets secondary to proximal renal tubular dysfunction (Fanconi syndrome) causing urinary wasting of glucose, amino acids, bicarbonate, phosphate, and electrolytes. Progressive glomerular damage leading to chronic kidney disease and eventually to End Stage Kidney Disease typically in the first decade, if untreated.^{[ citation needed ]}

By about age two, cystine crystals may also be present in the cornea. The buildup of these crystals in the eye causes an increased sensitivity to light (photophobia). ^[9] Without treatment, children with cystinosis are likely to experience complete kidney failure by about age ten. With treatment this may be delayed into the patients' teens or 20s. Other signs and symptoms that may occur in patients include muscle deterioration, blindness, inability to swallow, impaired sweating, decreased hair and skin pigmentation, diabetes, and thyroid and nervous system problems. ^[1]

The signs and symptoms of intermediate cystinosis are the same as nephropathic cystinosis, but they occur at a later age. Intermediate cystinosis typically begins to affect individuals around age twelve to fifteen. Malfunctioning kidneys and corneal crystals are the main initial features of this disorder. If intermediate cystinosis is left untreated, complete kidney failure will occur, but usually not until the late teens to mid twenties. ^[1]

People with non-nephropathic or ocular cystinosis do not usually experience growth impairment or kidney malfunction. The only symptom is photophobia due to cystine crystals in the cornea. ^[1]

Crystal morphology and identification

Cystine crystals are hexagonal in shape and are colorless. They are not found often in alkaline urine due to their high solubility. The colorless crystals can be difficult to distinguish from uric acid crystals which are also hexagonal. Under polarized examination, the crystals are birefringent with a polarization color interference. ^[18]

Pathophysiology

Nephropathic cystinosis is caused by pathogenic variants in the CTNS gene (encoding cystinosin), located on chromosome 17p13, which encodes a lysosomal membrane protein required for cystine transport out of lysosomes. ^[5] Loss of cystinosin function leads to intralysosomal accumulation of cystine crystals, which cause cellular dysfunction and apoptosis through mechanisms that include oxidative stress and impaired autophagy. The degree of residual cystinosin function correlates with disease severity, accounting for the spectrum from classic infantile to milder forms. ^[5]

Diagnosis

Clinical suspicion: ^[19]

Infants with Fanconi syndrome and failure to thrive; ophthalmologic findings (corneal crystals) support the diagnosis.

Measurement of leukocyte cystine levels: the diagnostic biochemical test is elevated cystine concentration in isolated white blood cells (leukocytes).

Genetic testing: molecular analysis of CTNS confirms the diagnosis and allows for carrier testing and prenatal diagnosis.

Additional testing: renal function and tubular markers, slit-lamp eye exam, thyroid function tests, and assessments for other systemic complications.

Complications

These complications often develop despite renal replacement therapy:

Ocular: corneal cystine crystal deposition causes photophobia, eye irritation, and decreased corneal sensitivity; crystals are visible on slit-lamp examination. ^[20]

Endocrine: hypothyroidism is common; growth hormone deficiency and diabetes mellitus may occur later. ^{[21] [22]}

Myopathy and swallowing difficulties from progressive proximal muscle weakness and distal involvement in adults. ^[23]

Neurologic: speech delay, cognitive impairment, and ataxia may appear in older children and adults. ^[24]

Other: hepatomegaly, pancreatitis, and gonadal dysfunction have been reported. ^{[25] [26] [27] [28]}

Genetics

Cystinosis has an autosomal recessive pattern of inheritance.

Cystinosis occurs due to a mutation in the gene CTNS, located on chromosome 17, which codes for cystinosin, the lysosomal cystine transporter. Symptoms are first seen at about 3 to 18 months of age with profound polyuria (excessive urination), followed by poor growth, photophobia, and ultimately kidney failure by age 6 years in the nephropathic form.^{[ citation needed ]}

All forms of cystinosis (nephropathic, juvenile and ocular) are autosomal recessive, which means that the trait is located on an autosomal chromosome, and only an individual who inherits two copies of the gene – one from both parents – will have the disorder. There is a 25% risk of having a child with the disorder, when both parents are carriers of an autosomal recessive trait.^{[ citation needed ]}

Cystinosis affects approximately 1 in 100,000 to 200,000 newborns. ^[1] and there are only around 2,000 known individuals with cystinosis in the world ^{[ citation needed ]}. The incidence is higher in the province of Brittany, France, where the disorder affects 1 in 26,000 individuals. ^[29]

Diagnosis

Cystinosis is a rare genetic disorder ^[30] that causes an accumulation of the amino acid cystine within cells, forming crystals that can build up and damage the cells. These crystals negatively affect many systems in the body, especially the kidneys and eyes. ^[3]

The accumulation is caused by abnormal transport of cystine from lysosomes, resulting in a massive intra-lysosomal cystine accumulation in tissues. Via an as yet unknown mechanism, lysosomal cystine appears to amplify and alter apoptosis in such a way that cells die inappropriately, leading to loss of renal epithelial cells. This results in renal Fanconi syndrome, ^[31] and similar loss in other tissues can account for the short stature, retinopathy, and other features of the disease.

Definitive diagnosis and treatment monitoring are most often performed through measurement of white blood cell cystine level using tandem mass spectrometry.^{[ citation needed ]}

Management

Current management aims to deplete intracellular cystine, treat renal tubular losses, preserve kidney function, and address systemic complications. ^[32]

Cysteamine therapy: Cysteamine (cysteamine bitartrate) is the only specific disease-modifying therapy. It enters lysosomes and reacts with cystine to form cysteine–cysteamine mixed disulfides that can exit the lysosome via alternative transporters, thereby lowering intralysosomal cystine. Oral cysteamine, started early and given lifelong, markedly reduces leukocyte cystine levels, delays progression to ESKD, and decreases some systemic complications. Both immediate-release and delayed-release formulations are used; adherence and dose optimization are critical. ^[7] Oral cysteamine therapy has extended the time to kidney failure by approximately 7 years (to a mean of 16 years) and mitigates or prevents late complications of the disease. In addition, cysteamine eyedrops can dissolve corneal cystine crystals within months. ^[8]

Supportive renal care: replacement of bicarbonate, phosphate, potassium, vitamin D and other supplements to manage Fanconi syndrome; growth monitoring and, when indicated, growth hormone therapy. ^{[33] [34] [35]}

Kidney transplantation: ESKD is managed with renal transplantation when necessary; however, transplantation does not correct systemic cystine accumulation, so cysteamine therapy should be continued after transplant. ^[36]

Ocular treatment: topical cysteamine eye drops reduce corneal crystal burden and symptoms. ^{[37] [20]}

Multidisciplinary follow-up: regular monitoring by nephrology, ophthalmology, endocrinology, neurology, nutrition, and other specialties is recommended to manage complications and optimize quality of life. ^{[38] [25]}

Treatment

Cystinosis is normally treated with cysteamine, which is available in capsules and in eye drops. ^[39] Cysteamine acts to solubilize the cystine by (1) forming a mixed disulfide cysteine-cysteamine and (2) reducing cystine to cysteine. People with cystinosis are also often given sodium citrate to treat the blood acidosis, as well as potassium and phosphorus supplements as well as others. If the kidneys become significantly impaired or fail, then treatment must be begun to ensure continued survival, up to and including renal transplantation. ^[40]

Investigational treatments

Gene therapy

Gene therapy for cystinosis focuses on replacing the defective CTNS gene, which encodes the lysosomal cystine transporter cystinosin. This approach aims to provide a potentially long-term or curative treatment.

• Autologous Hematopoietic Stem Cell Gene Therapy The most advanced gene therapy approach involves collecting a patient's own hematopoietic stem cells (HSCs), modifying them outside the body (ex vivo) to introduce a functional copy of the CTNS gene using a viral vector (e.g., lentivirus), and then reinfusing these modified cells back into the patient after chemotherapy. The modified HSCs are expected to engraft in the bone marrow, produce healthy blood cells, and deliver functional cystinosin throughout the body, thereby reducing cystine accumulation in various tissues.
• AVR-RD-04 (now DFT383 by Novartis) This investigational gene therapy, initially developed by AVROBIO in collaboration with the University of California, San Diego (UCSD), has shown promising preliminary results in Phase 1/2 clinical trials. It has received Orphan Drug and Rare Pediatric Disease designations from the FDA. Novartis acquired this program in May 2023 and has initiated a Phase I/II clinical trial (CYStem) recruiting children aged 2–5 years to evaluate its safety and efficacy. ^{[41] [42] [43] [ circular reference ] [44]}

CRISPR gene editing

CRISPR-Cas9 gene editing technology is being explored to directly correct the defective CTNS gene within a patient's own cells.

Research is underway to: ^{[45] [46]}

• Precisely insert repair templates into the genome to restore functional cystinosin. ^[45]
• Apply this technology to patient-derived pluripotent stem cells (iPSCs) to create kidney organoids for disease modeling and therapeutic testing, potentially leading to the replacement of defective kidney tubules with healthy, gene-edited ones. ^[46]

Pharmacological therapies (Beyond Cysteamine)

Researchers are also investigating novel pharmacological approaches to improve treatment for cystinosis.

• Cysteamine Prodrugs New formulations of cysteamine, such as prodrugs (inactive compounds metabolized into the active drug in the body), are being developed to improve patient adherence by overcoming the unpleasant smell and taste of existing medications and potentially allowing for less frequent dosing. For example, CF10 is in preclinical development with a Phase 1 clinical trial planned for 2025. ^[41]
• Combination Therapies Studies are identifying potential synergistic effects when combining cysteamine with other compounds. For instance, a combination of cysteamine and bicalutamide has shown promise in correcting the proximal tubule phenotype in in vitro models and cystinotic zebrafish, suggesting a novel dual-target pharmacological approach. ^{[47] [48]}
• Targeting Downstream Pathways Beyond directly reducing cystine accumulation, some therapies are exploring targeting "downstream" pathways or inflammatory mechanisms that contribute to organ damage in cystinosis. ^[41]

Prognosis

Before the invention of cysteamine treatment in the 1970's, ^[49] most children with classic nephropathic cystinosis reached end-stage chronic kidney disease (ESKD) by 10–12 years of age. ^[50] With early and continuous cysteamine therapy and modern supportive care, renal survival has improved substantially and many patients survive into adulthood, although they remain at risk for extra-renal complications that affect morbidity. ^[51]

Nevertheless, since cysteamine does not cure, but only slows down the disease progression, in many cases, the first kidney transplant in childhood/adolescence has to be followed by a second kidney transplant only 5-15 years later. ^[52]

History

Cystinosis was first described in the early 20th century by cystine crystal identification in tissues. ^[53] A historical case of cystinosis was originally termed Abderhalden–Kaufmann–Lignac syndrome (AKL syndrome), also called nephropathic cystinosis, which was observed to be an autosomal recessive renal disorder of childhood comprising cystinosis and renal rickets. It was named for Emil Abderhalden, Eduard Kaufmann and George Lignac. ^{[54] [55]} Affected children are developmentally delayed with dwarfism, rickets and osteoporosis. Renal tubular disease is usually present causing aminoaciduria, glycosuria and hypokalemia. Cysteine deposition is most evident in the conjunctiva and cornea.^{[ citation needed ]}

The CTNS gene was identified in the late 1990s, enabling genetic diagnosis and improved understanding of pathogenesis. ^[56]

See also

• Hartnup disease
• Cystinuria
• CTNS
• Cystinosin

References

1. "Cystinosis on Genetic home reference". Archived from the original on 2012-02-10. Retrieved 2011-04-01. This article incorporates text from this source, which is in the public domain .
2. "Abderhalden Kaufmann Lignac syndrome". rarediseases.info.nih.gov. Archived from the original on 15 May 2018. Retrieved 15 May 2018.
3. A. Gahl, William; Jess G. Thoene; Jerry A. Schneider (2002). "Cystinosis". N Engl J Med. 347 (2): 111–121. doi:10.1056/NEJMra020552. PMID   12110740.
4. Levtchenko, Elena; Emma, Francesco (2022), Blau, Nenad; Dionisi Vici, Carlo; Ferreira, Carlos R.; Vianey-Saban, Christine (eds.), "Cystinosis", Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, Cham: Springer International Publishing, pp. 1287–1294, doi:10.1007/978-3-030-67727-5_65, ISBN   978-3-030-67726-8 , retrieved 2025-12-21
5. NCBI Bookshelf. GeneReviews: Cystinosis. GeneReviews® [Internet]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1409/
6. MedlinePlus Genetics. Cystinosis. U.S. National Library of Medicine. Available from: https://medlineplus.gov/genetics/condition/cystinosis/
7. National Organization for Rare Disorders (NORD). Cystinosis. Available from: https://rarediseases.org/rare-diseases/cystinosis/
8. Chang, Hayley E.; Hossain, Mahin S.; Song, Chris; Surampudi, Narayana; Nesterova, Galina; Gahl, William A. (2025-05-14). "Long-term outcomes in nephropathic cystinosis: a review". Pediatric Nephrology. doi:10.1007/s00467-025-06790-6. ISSN   0931-041X. PMID   40369127.
9. Cherqui, Stéphanie; Courtoy, Pierre J. (2017). "The renal Fanconi syndrome in cystinosis: pathogenic insights and therapeutic perspectives". Nature Reviews Nephrology. 13 (2): 115–131. doi:10.1038/nrneph.2016.182. PMC   5116501 . PMID   27890970.
10. Nesterova G, Gahl WA. Cystinosis: the evolution of a treatable disease. Pediatr Nephrol 2012;28:51–9.
11. Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med 2002;347:111-121.
12. Kumar A, Bachhawat AK. A futile cycle, formed between two ATP-dependent γ-glutamyl cycle enzymes, γ-glutamyl cysteine synthetase and 5-oxoprolinase: the cause of cellular ATP depletion in nephrotic cystinosis?; J Biosci 2010;35:21–25.
13. Park MA, Thoene JG. Potential role of apoptosis in development of the cystinotic phenotype. Pediatr Nephrol 2005;20:441–446.
14. Besouw M, Masereeuw R, Van den Heuvel L et al. Cysteamine: an old drug with new potential. Drug Discov Today 2013.
15. Haffner, Dieter; Leifheit-Nestler, Maren; Alioli, Candide; Bacchetta, Justine (2022-01-05). "Muscle and Bone Impairment in Infantile Nephropathic Cystinosis: New Concepts". Cells. 11 (1): 170. doi: 10.3390/cells11010170 . ISSN   2073-4409. PMC   8749987 . PMID   35011732.
16. Bäumner, Sören; Weber, Lutz T. (2018-03-14). "Nephropathic Cystinosis: Symptoms, Treatment, and Perspectives of a Systemic Disease". Frontiers in Pediatrics. 6 58. doi: 10.3389/fped.2018.00058 . ISSN   2296-2360. PMC   5861330 . PMID   29594088.
17. Biswas, Susmito; Gaviria, Martha; Malheiro, Luísa; Marques, João Pedro; Giordano, Vincenzo; Liang, Hong (December 2018). "Latest Clinical Approaches in the Ocular Management of Cystinosis: A Review of Current Practice and Opinion from the Ophthalmology Cystinosis Forum". Ophthalmology and Therapy. 7 (2): 307–322. doi:10.1007/s40123-018-0146-6. ISSN   2193-8245. PMC   6258572 . PMID   30242621.
18. Spencer, Daniel. "Cystine". CRYSTALS. Urinalysis (Texas Collaborative for Teaching Excellence). Archived from the original on 6 November 2016. Retrieved 4 March 2012.
19. "Pädiatrische Nephrologie". Monatsschrift Kinderheilkunde (in German). 155 (3): 293–303. March 2007. doi:10.1007/s00112-007-1486-9. ISSN   0026-9298.
20. Dhiman, Shweta; Mahapatra, Santosh K; Parhi, Anjalika; Shree, Pallavi; Jain, Parul (April 2024). "Ocular cystinosis – Clinical presentation and review of the literature". Indian Journal of Ophthalmology - Case Reports. 4 (2): 444–448. doi: 10.4103/IJO.IJO_1944_23 . ISSN   2772-3070.
21. Lucky, Anne W.; Howley, Peter M.; Megyesi, Klara; Spielberg, Stephen P.; Schulman, Joseph D. (August 1977). "Endocrine studies in cystinosis: Compensated primary hypothyroidism". The Journal of Pediatrics. 91 (2): 204–210. doi:10.1016/S0022-3476(77)80813-5. PMID   406375.
22. Fivush, Barbara (1987-10-01). "Pancreatic Endocrine Insufficiency in Posttransplant Cystinosis". Archives of Pediatrics & Adolescent Medicine. 141 (10): 1087–1089. doi:10.1001/archpedi.1987.04460100065027. ISSN   1072-4710. PMID   3307383.
23. Sadjadi, Reza; Ghossein, Cybele; Elenberg, Ewa (2025-07-07). "Clinical perspectives on myopathic complications in nephropathic cystinosis". Journal of Rare Diseases. 4 (1) 37. doi:10.1007/s44162-025-00092-z. ISSN   2731-085X.
24. Trauner, Doris A (2010-04-29), Nass, MD, Ruth; Frank, MD, Yitzchak (eds.), "Neurological and Cognitive Consequences of Nephropathic Cystinosis", Cognitive and Behavioral Abnormalities of Pediatric Diseases, Oxford University PressNew York, pp. 333–341, doi:10.1093/oso/9780195342680.003.0039, ISBN   978-0-19-534268-0 , retrieved 2025-12-22
25. Nesterova, Galina; Gahl, William (June 2008). "Nephropathic cystinosis: late complications of a multisystemic disease". Pediatric Nephrology. 23 (6): 863–878. doi:10.1007/s00467-007-0650-8. ISSN   0931-041X. PMID   18008091.
26. Gahl, William A.; Nesterova, Galina (2016), Avner, Ellis D.; Harmon, William E.; Niaudet, Patrick; Yoshikawa, Norishige (eds.), "Cystinosis and Its Renal Complications in Children", Pediatric Nephrology, Berlin, Heidelberg: Springer Berlin Heidelberg, pp. 1329–1353, doi:10.1007/978-3-662-43596-0_37, ISBN   978-3-662-43595-3 , retrieved 2025-12-22
27. Treikauskas, U.; Zerell, K.; Harms, E.; Aghayan–Ugurluoglu, R.; Brangenberg, R.; Herzig, N.; Hintner, H.; Knerr, C.; Köppl, C.; Landthaler, I.; Marquardt, T.; Passow, M.; Rausch, A.; Römer, U.; Steidle, G. (2016-11-01). "Nephropathische Cystinose: Spätkomplikationen einer Multisystemerkrankung – Langzeitergebnisse der interdisziplinären Cystinose-Sprechstunde in Traunstein". Nieren- und Hochdruckkrankheiten. 45 (11): 432–438. doi:10.5414/NHX01812. ISSN   0300-5224.
28. Kasimer, Rachel Nora; Langman, Craig B (February 2021). "Adult complications of nephropathic cystinosis: a systematic review". Pediatric Nephrology. 36 (2): 223–236. doi:10.1007/s00467-020-04487-6. ISSN   0931-041X. PMID   32016627.
29. Kalatzis, V; Cherqui S; Jean G; Cordier B; Cochat P; Broyer M; Antignac C (October 2001). "Characterization of a putative founder mutation that accounts for the high incidence of cystinosis in Brittany" . J Am Soc Nephrol. 12 (10): 2170–2174. doi: 10.1681/ASN.V12102170 . PMID   11562417. Archived from the original on 14 February 2015. Retrieved 31 March 2011.
30. "Cystinosis". Archived from the original on 2011-07-18. Retrieved 2008-07-20.
31. Howard G. WORTHEN; Robert A. GOOD (1958). "The de Toni-Fanconi Syndrome with Cystinosis". Am J Dis Child. 95 (6): 653–688. doi:10.1001/archpedi.1958.02060050657011. PMID   13532161.
32. Lu, D. L., Teo, S. S. L., & Yap, H. K. (2021). "Management of Nephropathic Cystinosis". In Pediatric Nephrology: On-The-Go: (Fourth Edition) (pp. 292-302). World Scientific Publishing Co. https://www.scopus.com/inward/record.uri?eid=2-s2.0-85138866047&partnerID=40&md5=c14be2113deb72f3efbf7c43d86bb2ee .{{cite book}}: External link in |title= (help)
33. Todisco, Tommaso; Ubertini, Grazia Maria; Bizzarri, Carla; Loche, Sandro; Cappa, Marco (2024-07-01). "Chronic Kidney Disease and Growth Failure in Children". Children. 11 (7): 808. doi: 10.3390/children11070808 . ISSN   2227-9067. PMC   11274908 . PMID   39062256.
34. Guzzetti, Chiara; Ibba, Anastasia; Incandela, Valeria; Loche, Sandro (2024-12-24). "GH Therapy in Non–Growth Hormone-Deficient Children". Children. 12 (1): 3. doi: 10.3390/children12010003 . ISSN   2227-9067. PMC   11764098 . PMID   39857834.
35. Harms, Erik (2006), Blau, Nenad; Leonard, James; Hoffmann, Georg F.; Clarke, Joe T. R. (eds.), "Cystinosis", Physician's Guide to the Treatment and Follow-Up of Metabolic Diseases, Berlin/Heidelberg: Springer-Verlag, pp. 221–229, doi:10.1007/3-540-28962-3_23, ISBN   978-3-540-22954-4 , retrieved 2025-12-21
36. Killeen, Trevor F.; Elfering, Sarah L.; Riad, Samy M.; Linden, Michael A.; Leng, Ethan Y.; Kandaswamy, Raja; Kizilbash, Sarah J.; Chavers, Blanche M.; Harmon, James V. (September 2022). "Nephropathic cystinosis in a kidney transplant recipient: A mesenteric lymph node demonstrates positive birefringent crystals". Human Pathology Reports. 29 300661. doi:10.1016/j.hpr.2022.300661.
37. Liang, Hong; Baudouin, Christophe; Giordano, Vincenzo (April 2025). "Evaluation of a new classification system for measuring the progression of ocular cystinosis: an analysis of 64 patients". British Journal of Ophthalmology. 109 (4): 442–449. doi:10.1136/bjo-2023-325093. ISSN   0007-1161. PMC   12013570 . PMID   39357989.
38. Levtchenko, Elena; Servais, Aude; Hulton, Sally A; Ariceta, Gema; Emma, Francesco; Game, David S; Lange, Karin; Lapatto, Risto; Liang, Hong; Sberro-Soussan, Rebecca; Topaloglu, Rezan; Das, Anibh M; Webb, Nicholas J A; Wanner, Christoph (2022-08-22). "Expert guidance on the multidisciplinary management of cystinosis in adolescent and adult patients". Clinical Kidney Journal. 15 (9): 1675–1684. doi:10.1093/ckj/sfac099. ISSN   2048-8505. PMC   9394719 . PMID   36003666.
39. Besouw, Martine; Masereeuw, Rosalinde; Van Den Heuvel, Lambert; Levtchenko, Elena (2013). "Cysteamine: An old drug with new potential". Drug Discovery Today. 18 (15–16): 785–792. doi:10.1016/j.drudis.2013.02.003. PMID   23416144.
40. Nesterova, Galina; Gahl, William A. (October 6, 2016). "Cystinosis". GeneReviews. University of Washington, Seattle. PMID   20301574. Archived from the original on April 5, 2011. Retrieved January 11, 2017.
41. Goodyer, P.; Torban, E. (20 May 2025). "Emerging therapeutic strategies for cystinosis - Frontiers". Frontiers in Pediatrics. 13. doi: 10.3389/fped.2025.1601409 . PMC   12135878 . PMID   40469087.
42. "Phase I/II CYStem clinical trial - Cystinosis Network Europe" . Retrieved 2024-05-28.
43. "DFT383 - Wikipedia" . Retrieved 2024-05-28.
44. "Stem Cell Gene Therapy for Cystinosis - SCGE Platform" . Retrieved 2024-05-28.
45. Sendino Garví, E.; Faria, J.; Pou Casellas, C.; Thijssen, S.; Wubbolts, E.J.; Jamalpoor, A.; Harrison, P.; Masereeuw, R.; Janssen, M.J. (2023). "Gene surgery as a potential treatment option for Nephropathic Cystinosis in vitro". doi:10.1101/2023.11.01.565117 . Retrieved 2024-05-28.
46. "Stem cell study reveals how infantile cystinosis causes kidney failure – and how to cure it" . Retrieved 2024-05-28.
47. Jamalpoor, A.; Van Gelder, C. A.; Yousef Yengej, F. A.; Zaal, E. A.; Berlingerio, S. P.; Veys, K. R.; Pou Casellas, C.; Voskuil, K.; Essa, K.; Ammerlaan, C. M.; Rega, L. R.; Van Der Welle, R. E.; Lilien, M. R.; Rookmaaker, M. B.; Clevers, H.; Klumperman, J.; Levtchenko, E.; Berkers, C. R.; Verhaar, M. C.; Altelaar, M.; Masereeuw, R.; Janssen, M. J. (2021). "Cysteamine–bicalutamide combination therapy corrects proximal tubule phenotype in cystinosis - PMC - PubMed Central". EMBO Molecular Medicine. 13 (7) e13067. doi:10.15252/emmm.202013067. PMC   8261496 . PMID   34165243.
48. Sur, S.; Kerwin, M.; Pineda, S.; Sansanwal, P.; Sigdel, T. K.; Sirota, M.; Sarwal, M. M. (2025). "Novel mechanism for tubular injury in nephropathic cystinosis - eLife". eLife. 13. doi: 10.7554/eLife.94169 . PMC   11925453 . PMID   40111391.
49. Thoene, Jess G. (2010-08-23), "Cysteamine treatment of nephropathic cystinosis", Small Molecule Therapy for Genetic Disease, Cambridge University Press, pp. 101–113, doi:10.1017/cbo9780511777905.009, ISBN   978-0-521-51781-2 , retrieved 2025-12-21
50. Broyer, M. (2000). "[Cystinosis from childhood to adulthood]". Nephrologie. 21 (1): 13–18. ISSN   0250-4960. PMID   10730275.
51. Helmy, Rasha; Atia, Fatma M.; Soliman, Neveen A. (2025-04-07). "Native kidney and graft survival in a cohort of Egyptian children with nephropathic cystinosis: national referral center experience". Italian Journal of Pediatrics. 51 (1) 110. doi: 10.1186/s13052-025-01943-7 . ISSN   1824-7288. PMC   11977944 . PMID   40197488.
52. Carter, Jade (2018-03-02). "Waiting for my second kidney transplant in 7 years". Journal of Kidney Care. 3 (2): 120–121. doi:10.12968/jokc.2018.3.2.120. ISSN   2397-9534.
53. Kroll, Wolfgang; Lichte, Karl-Henning (November 1973). "Cystinosis: A review of the different forms and of recent advances". Humangenetik. 20 (2): 75–87. doi:10.1007/BF00284842. ISSN   0340-6717. PMID   4594235.
54. B.G. Firkin & J.A.Whitworth (1987). Dictionary of Medical Eponyms. Parthenon Publishing. ISBN   1-85070-333-7
55. "Who Named It?". Archived from the original on 2019-03-01. Retrieved 2024-03-01.
56. Attard, M.; Jean, G.; Forestier, L.; Cherqui, S.; van't Hoff, W.; Broyer, M.; Antignac, C.; Town, M. (1999-12-01). "Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin". Human Molecular Genetics. 8 (13): 2507–2514. doi:10.1093/hmg/8.13.2507. ISSN   0964-6906. PMID   10556299.

External links

• Cystinosis at NLM Genetics Home Reference
• GeneReviews/NCBI/NIH/UW entry on Cystinosis