• Users Online: 108
  • Print this page
  • Email this page

 Table of Contents  
Year : 2022  |  Volume : 7  |  Issue : 2  |  Page : 67-72

Cystinosis and kidney: What do we know about it?

1 Department of Pediatric Nephrology, Square Hospitals Ltd, Shahbagh, Bangladesh
2 Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University, Shahbagh, Bangladesh
3 Department of Pediatric Nephrology, Anwer Khan Modern Medical College Hospital, Dhanmondi, Dhaka, Bangladesh

Date of Submission12-Feb-2022
Date of Acceptance13-Jul-2022
Date of Web Publication22-Nov-2022

Correspondence Address:
Dr. Md Abdul Qader
Square Hospitals Ltd, 18/F, Bir Uttam Qazi Nuruzzaman Sarak, West Panthapath, Dhaka-1205
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pnjb.pnjb_6_22

Rights and Permissions

Cystinosis is the most common cause of renal Fanconi syndrome caused by defective CTNS gene resulting accumulation of cystine in the lysosomes of multiple organs of the body. Although Cystinosis can affect multiple organs, but kidney is the primary organ affected. After kidney, it affects eyes and can cause retinopathy and blindness. Patients can have hypothyroidism, diabetes mellitus and gonadal dysfunction in males secondary to cystine crystal deposition in thyroid, pancreas, and gonads respectively. The most common form is the infantile nephropathic cystinosis may presents with features of Fanconi syndrome. Other rare forms include juvenile form which have mild Fanconi syndrome and adult-onset ocular form of cystinosis. Diagnosis of cystinosis can be confirmed by a slit lamp examination to find corneal cystine crystal deposition, genetic tests for CTNS gene and leukocyte cystine level both for diagnosis and monitoring of the therapy. Children with cystinosis need specific therapy to delay the progression of the disease with the advancement of clinical research, newer therapies are under clinical trial and hematopoietic stem cell transplantation shows promising results including improvement of kidney structure and Fanconi syndrome.

Keywords: CTNS gene, cysteamine, cystinosis, fanconi syndrome, hematopoietic stem cell transplantation

How to cite this article:
Qader MA, Huque SS, Hanif M. Cystinosis and kidney: What do we know about it?. Paediatr Nephrol J Bangladesh 2022;7:67-72

How to cite this URL:
Qader MA, Huque SS, Hanif M. Cystinosis and kidney: What do we know about it?. Paediatr Nephrol J Bangladesh [serial online] 2022 [cited 2023 Oct 4];7:67-72. Available from: http://www.pnjb-online.org/text.asp?2022/7/2/67/361621

  Introduction Top

Cystinosis is a lysosomal storage disorder which is inherited as an autosomal recessive manner. It is caused by defective CTNS (17p 13.2) gene which encodes a carrier protein namely cystinosin.[1] Cystinosin is responsible for lysosomal cystine transport across the cell membrane to the cytoplasm and the result of defective CTNS gene is accumulation of cystine in the lysosomes of different organs. Though it is a multisystem disease, kidneys are the primary organ especially proximal tubular cells that usually have cystine crystal deposition during the early stages of life. In recent years it was found in the CTNS knockout mice that cystine crystal can be deposited in the kidney even before birth.[2]

Cystinosis has 3 forms namely infantile nephropathic cystinosis, juvenile onset nephropathic cystinosis and adult onset ocular cystinosis.[3]

Considering the rarity of cystinosis, the diagnosis is often late and in some cases the diagnosis is made when they present with end stage kidney disease (ESKD). The infantile nephropathic cystinosis if left untreated can progressed to ESKD in the first decades of life.[4] The renal progression in the juvenile nephropathic cystinosis is much slower than the former. There is potential development in the treatment of cystinosis day by day but the early diagnosis and initiation of appropriate treatment is always challenging. The lack of diagnostic facilities, particularly genetic testing, causes diagnosis to be delayed, particularly in developing countries. The costs of medicine, including eye drops and oral medications, are high and, in most cases, out of reach for parents from developing countries.

Here we have reviewed the epidemiology, pathogenesis, disease course and treatment of cystinosis. We have tried to find the potential future research areas in relation to improve care of the children with cystinosis.

  Epidemiology Top

The incidence of cystinosis is varied between 1 in 100,000 to 200,000 live births among the general population but a higher rate was reported among French Brittany (1 in 2600 live births) and Saguenay-Quebec (1 in 62500 live births) because of distinct mutations in the CTNS gene (c.898–900 + 24del127 and p.Trp138X respectively).[5],[6],[7] Cystinosis comprises a small number of patients among the chronic kidney disease population; however a precise data on prevalence are lacking. Cystinosis comprises about 1.4% among children on dialysis and 2.1% among kidney transplant recipient according to NAPRTCS (North American Pediatric Renal Trials and Collaborative Studies) 2011 and 2014 data.[8]

  Pathogenesis Top

The pathogenesis of cystinosis is complex and difficult to understand. There are two main forms of cystine that accumulates in the different organ namely soluble cystine and cystine crystal. Primarily a soluble cystine builds up in the proximal tubular cells and interstitial macrophages of the kidney and then organized into a polyhedral crystal. In children, the crystals are typically found in the interstitial macrophages of various organs. In CTNS mutant mice, cystine crystals were found in the proximal tubular cells and there is evidence of Fanconi syndrome long before crystal formation in CTNS knock out mice’s kidney.[2] Cystine crystals deposition in the kidney causes fibrosis which leads to progressive kidney failure.[9]

Cystine crystal deposition starts from the tubuloglomerular junction and slowly progress to the proximal tubule and cause apoptosis of proximal tubular cells. By this process of progressive apoptosis, the thick columnar cells of the proximal tubules are then replaced by the flat epithelium of the Bowman’s capsule (known as sliding metaplasia). This epithelial metaplasia eventually leads to swan neck deformity of the proximal tubules.

There is decrease expression of apical endocytic receptor, megalin and cubilin in the proximal tubular cells of the CTNS knockout mice. Megalin and cubilin are responsible for reuptake of lysosomal degradation of protein. The deficiency of Megalin and cubilin in the proximal tubular cells results in low molecular weight proteinuria.[10],[11]

Cystine is the main source of cysteine which is used for the synthesis of glutathione in the cytosol. The mechanism for Fanconi syndrome is proposed as the deficiency of glutathione inside the cell as the major cystosolic antioxidant along with neutralization of free radicals like oxygen species. There is reduced adenosine triphosphate (ATP) in the tubular cells of individual with cystinosis compared to normal tubular cells likely due to altered cellular energy homeostasis.[12] Treatment with cysteamine can effectively decrease apoptotic cell death and cell oxidation in vivo but is unable to reverse Fanconi syndrome.[13]

Cystine crystal deposition in the eyes can be seen by slit lamp exam from the age of 12 months and are always present by the age of 18 months. It also causes superficial punctuate and filament keratopathy, peripheral corneal neovascularisation and posterior synechiae with thickened iris.[14] There is pigment epithelial mottling and depigmentation seen in the retina which leads to retinopathy and blindness in 10–15% cases.[15]

Cystine crystal formation and accumulation in the thyroid follicles leads to fibrosis and atrophy of the gland which causes primary hypothyroidism. The clinical manifestations of hypothyroidism are evident by the second decades of life.[16]

  Clinical Presentation Top

There are three clinical forms of cystinosis. According to age of presentation, infantile cystinosis is the most common form and can present as early as 6 month age with features of renal Fanconi syndrome. Extra renal manifestations include involvement of eyes, endocrine disorders, musculoskeletal, neurocognitive as well as pulmonary disorder.[3] Juvenile forms of nephropathic cystinosis usually have a milder presentation and adult onset cystinosis have isolated ocular manifestation and rarely diagnosed before adulthood.[3]

  • 1) Infantile nephropathic cystinosis: Infantile nephropathic cystinosis is almost 95% of the cystinosis and it is caused by severe truncating mutations of both the allele of CTNS gene.[1],[17] Children with infantile form are normal at birth and they began to present with features of Fanconi syndrome at the age of 6–9 months.[18] It is the most severe form of cystinosis and if left untreated, the renal function usually starts to deteriorate at 5–6 years of age and children eventually progress to end-stage kidney disease (ESKD) by ~10 years of age.[1]

  • 2) Late-onset Juvenile nephropathic cystinosis: Juvenile form has been described with a milder mutation in at least one allele of CTNS gene. It is usually diagnosed in late childhood or in the adolescence period. The juvenile form presents with either isolated proteinuria or milder form of Fanconi syndrome.

  • 3) Adult-onset, ocular form of cystinosis: Adult form of cystinosis presents with symptoms related to corneal cystine deposition. There is milder mutations in at least one of the allele are observed. It has no kidney involvement and very mild disease which rarely diagnosed before adulthood.

The Fanconi syndrome manifests as features proximal renal tubular acidosis such as polyuria, polydipsia, failure to thrive, vomiting, constipation, growth failure, and or rickets. Other features of Fanconi syndromes include biochemical features of proximal tubular dysfunction such as normal anion gap metabolic acidosis with proteinuria and Phosphaturia. Older patients might have blurred vision due to cystine crystal deposition in the eye, nocturnal enuresis secondary to polyuria and pathological fracture due to rickets.[19],[20]

Growth failure and failure to thrive is one of major findings in the early childhood. People with cystinosis have normal birth weight and length. They tend to develop growth failure by the age of 6months to 12 months and height fall to 3rd centile by then.[21] If specific therapy with cysteamine was not started before one year of age, the growth curve remains bellow third centile.[3] There is Phosphaturia, calciuria, increased urinary losses of vitamin D binding protein and decrease vitamin D conversion in the kidney secondary to decrease activity of alpha-1 hydroxylase in the proximal tubules leads to vitamin D resistant hypophosphatemic rickets.[22]

Eye changes

Crystal accumulation in the conjunctiva and cornea is the pathognomonic ophthalmic manifestation of cystinosis [Figure 1]. Corneal crystals present as myriad of needle-shaped, highly reflective opacities leads to photophobia, recurrent corneal erosion usually presents after the first year of life. The crystals can easily be seen by slit lamp examination. If left untreated, the crystal deposition can cause retinopathy and blindness as early as 3 years of age.[23]
Figure 1: Evidence of Cystine crystals deposition in the conjunctiva, cornea, and fundus of the eye on slit-lamp examination. (Photo by Prof Nuzhat Choudhury, Prof of Ophthalmology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh)

Click here to view

Endocrine abnormalities include hypothyroidism related to fibrosis of thyroid follicular cells by cystine crystals. Cystine crystal deposition can impair gonadal function in males but pubertal development is achieved with testosterone therapy but infertility is variable.[24],[25] But females have normal gonadal functions and there are reports of successful pregnancy.[26] Insulin-dependent diabetes mellitus secondary to pancreatic dysfunction are seen in the second or third decades of life.[27]

Neurological features starts with muscle weakness and wasting of hand muscles in the form of progressive ischemic myopathy.[28] If the cystine depletion is suboptimal, patient may present with features of encephalopathy and stroke. Children who have fine motor in coordination can be persistent in adult life.[29]

  Diagnosis Top

Diagnosis of cystinosis is often challenging as patients might be misdiagnosed as a case of distal renal tubular acidosis in early stage. The diagnosis is made on the basis of clinical and biochemical features of proximal renal tubular acidosis. A confirmation of the diagnosis of cystinosis can be made with the following tests.[30]

  • 1) Presence of corneal cystine crystals in slit lamp examination.

  • 2) Leukocyte cystine level: Measurement of leukocyte cystine level is useful for diagnosis. A level more 2nmol half cystine/mg protein is diagnostic (Normal level is less than 0.2nmol half cystine in slit lamp exam). The cost of test is about USD200 in the nearest lab of India.

  • 3) Genetic tests for either CTNS gene or whole exome sequencing. The costs are USD 340 for CTNS gene and USD 470 for whole exome sequencing in the nearest lab of India.

  • 4) Prenatal diagnosis with DNA samples from chorionic villi or from amniotic fluid cells.[31]

  Treatment Top

  • a) Dietary management: Children with cystinosis should receive 100% of the recommended dietary allowance (RDA) of calories for their age composed of a balanced diet schedule including salt and fluid supplements. Very young children those who have frequent vomiting and are at risk of growth failure, early placement of gastric tube as well as jejunal tubes for feeding is advised.

  • b) Cysteamine: Cysteamine was first approved for human use in USA in the year 1994. Cysteamine can delay the progression of kidney failure by reducing leukocyte cystine level. Cysteamine via amino-thiol transporter enters into the lysosome and cleaves cystine to cysteine or cysteine-cysteamine mixed disulfide cysteine. Then cysteine-cysteamine exits lysosome via lysine carrier. Cysteamine is available as cysteamine bitartrate (Cystagon or Procysbi).
    • 1) Cystagon is a short acting medication and is taken orally every 6 hourly.
      • i. The target dose is 1.3 mg/m2/day of the free base (<12years) and 2g/m2/day (>12years or weighing >50Kg). The starting dose should be one-sixth of the target dose and gradually increase the dose over 4–6 weeks. The maximum dose should not be exceeded 1.95 mg/m2/day.

    • 2) Procysbi® is given orally two times daily and a starting dose for cysteamine naïve patients is 0.2 to 0.3g/m2/day.

    • 3) Topical Cysteamine hydrochloride eye drops are available as 0.44% cysteamine ophthalmic solution (Cystaran) and 0.55% Cysteamine gel (Cystadrops) which are used for dissolving the crystals and for relief of symptoms.

Adverse drug events include foul odor, diarrhea, gastrointestinal upset and headache which are a major burden for achieving compliance.

  • c) Other potential treatment options[1]:
    • 1) Indomethacin can enhance salt reabsorption and improvement of polyuria and other clinical symptoms by decreasing the expression of aquaporin-2. Indomethacin can be given orally at a dose of 1-3 mg/kg/day in 2–3 divided doses. But long term use of it raises concern of chronic indomethacin toxicity.

    • 2) Renin-angiotensin system blockade: Reducing albuminuria using angiotensin-converting enzyme inhibitor (ACEi) and or angiotensin receptor blocker (ARB) is helpful in delaying progressing of renal function but there is lack of clinical evidence to use this therapy in children with Fanconi syndrome.

    • 3) Correction of electrolyte imbalance and alkalinization with citrate (Polycitra, Bicitra, or Potassium citrate). Also correction of hyponatermia and hypokalemia.

    • 4) Treatment with phosphate and vitamin D supplement for prevention of rickets and pathological fracture.

  • d) Treatment of endocrine abnormalities[32]:

    • 1) Treatment of hypothyroidism along with growth hormone therapy.

    • 2) Treatment of diabetes mellitus with insulin therapy.

    • 3) Testosterone replacement for male hypogonadism.

  • e) Renal Replacement therapy- Kidney transplantation:

The proximal tubular abnormality abnormalities secondary cystinosis does not recur in the transplanted kidney but the metabolic abnormalities related to Fanconi syndrome may persist if the native kidney continues to produce urine. Still kidney transplantation is the best choice for children with kidney failure and overall outcome of kidney transplantation is better in children with cystinosis compared to other patients.[33]

  Potential New Treatments Top

1) Hematopoietic stem cell transplantation

Irradiated CTNS knockout mice was transplanted with either purified mesenchymal stem cells (MSC) or hematopoietic stem cells (HSC) to repopulate the bone marrow with CTNS carrying donor cells. The results were promising and it showed HSC lead to a long term improvement in kidney structure and Fanconi syndrome.[34] The proposed mechanism is the bone marrow derived macrophages engrafted in cystinotic kidney generate nanotubular extensions, which are readily crosses the tubular basemetn membrane and deliver cystinosis into diseased proximal tubule cells.[35] Similar results also observed in other organs including eye and thyroid after HSC.

2) Genistein

Ganistein is an angiogenesis inhibitor and a phytoestrogen which is found in soy product, e.g. soybeans and soy milk. Genistein can decrease intracellular cysteine level and enlargement of lysosomes along with rescue the endocytosis defect by activating transcriptor factor EB in the proximal tubular cells of the cystinotic kidney. Genistein is previously been proven to be used for depleting lysosomal storage of glycosaminoglycans in mucopolysaccharidosis in vivo and has shown improvement of cognition of the affected.[36]

3) ELX-02

ELX-02 is eukaryotic ribosomal selective glycosides (ERSG) which enhance production of functional protein to restore activity. ELX- 02 can effectively reduce white cell cystine level and the trial is been currently suspended because of revision of trial design to include children older than 12years.[37],[38]

4) Current trials for stem cell transplantation

The current clinical trial of HSC of gene modified own stem cell (ex vivo gene- modified with a lentiviral vector, pCCL-CTNS to express CTNS gene product name: CTNS-RD-04) running which includes adolescent and adult patients with cystinosis.[39]

  Outcome Top

Outcome of cystinosis who were treated with cysteamine is promising and a recent multicentre study including 453 nephropathic cystinosis patient has shown it has a major influence on improving kidney function and delay progression to ESRD.[40]

  Potential Research Areas Top

With the recent advancements of research, several aspects in the pathogenesis and therapeutic goal have come up and have created uncertain areas in cystinosis patient management.

The role of cystine crystals in the pathogenesis of interstitial fibrosis is still unknown. Moreover, with the treatment of cysteamine, the changes in the proximal tubular cells are irreversible and recent research revealed there is an abnormal mTORC1 activation which also contributes to the PTC damage.[41] So, details of the pathogenic mechanisms and therapeutic options for these are still unknown. The role of early administration of cysteamine from birth in preventing renal Fanconi syndrome is still unknown.

Some children show severe proteinuria without renal Fanconi syndrome.[42] So details of podocyte involvements in cystinosis are still unknown. Regarding treatments options, adverse events profile and compliance to cysteamine are bringing up the necessity of therapeutic alternatives to this medication. The toxicity related to lifetime use of cysteamine is unknown and use during pregnancy and lactation is still debatable. The timing of sperm harvesting and preservation for future use in male cystinosis patients is still unknown.[25]

  Conclusion Top

With the advancement of clinical research the treatment options are widening day by day. Cysteamine is an effective drug that decreases intracellular cystine level and delay in progression of kidney failure. Newer agents like Genistein and ELX-02 are promising but HSC transplantation can improve proximal tubular changes and kidney function.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Emma F, Nesterova G, Langman C, Labbe A, Cherqui S, Goodyer P, et al. Nephropathic cystinosis: An international consensus document. Nephrol Dial Transplant 2014;29:v87-94.  Back to cited text no. 1
Broyer M, Guillot M, Gubler MC, Habib R Infantile cystinosis: A reappraisal of early and late symptoms. Adv Nephrol Necker Hosp 1981;10:137-66.  Back to cited text no. 2
Wilmer MJ, Schoeber JP, van den Heuvel LP, Levtchenko EN Cystinosis: Practical tools for diagnosis and treatment. Pediatr Nephrol 2011;26:205-15.  Back to cited text no. 3
Nesterova G, Gahl W Nephropathic cystinosis: Late complications of a multisystemic disease. Pediatr Nephrol 2008;23:863-78.  Back to cited text no. 4
Levy M, Feingold J Estimating prevalence in single-gene kidney diseases progressing to renal failure. Kidney Int 2000;58:925-43.  Back to cited text no. 5
Braekeleer MD Hereditary disorders in Saguenay- Lac- St- Jene (Quebec, Canada). Hum Hered 1991;41:141-6.  Back to cited text no. 6
McGowan- Jordan J, Stoddard K, Podolsky L, Orrbine E, McLaine P, Town M, et al. Molecular analysis of cystinosis: Probable irish origin of the most common french canadian mutations. Eur J of Hum Genet 1999;7:671-8.  Back to cited text no. 7
North American Pediatric Renal Trials and Collaborative Studies. NAPRTCS Annual Reports. NAPRTCS Online [online], https://naprtcs.org/registries/annual-report [Last accessed on 4th June 2022].  Back to cited text no. 8
Prencipe G, Caiello I, Cherqui S, Whisenant T, Petrini S, Emma F, et al. Inflammasome activation by cystine crystals: Implications for the pathogenesis of cystinosis. J Am Soc Nephrol 2014;25:1163-9.  Back to cited text no. 9
Raggi C, Luciani A, Nevo N, Antignac C, Terryn S, Devuyst O Dedifferentiation and aberrations of the endolysosomal compartment characterize the early stage of nephropathic cystinosis. Hum Mol Genet 2014;23:2266-78.  Back to cited text no. 10
Ivanova EA, De Leo MG, Van Den Heuvel L, Pastore A, Dijkman H, De Matteis MA, et al. Endo-lysosomal dysfunction in human proximal tubular epithelial cells deficient for lysosomal cystine transporter cystinosin. Plos One 2015;10:e0120998.  Back to cited text no. 11
Cherqui S, Courtoy PJ The renal fanconi syndrome in cystinosis: Pathogenic insights and therapeutic perspectives. Nat Rev Nephrol 2017;13:115-31.  Back to cited text no. 12
Levtchenko EN, Wilmer MJ, Janssen AJ, Koenderink JB, Visch HJ, Willems PH, et al. Decreased intracellular Atp content and intact mitochondrial energy generating capacity in human cystinotic fibroblasts. Pediatr Res 2006;59:287-92.  Back to cited text no. 13
Tsilou ET, Rubin BI, Reed GF, Iwata F, Gahl W, Kaiser-Kupfer MI Age-related prevalence of anterior segment complications in patients with infantile nephropathic cystinosis. Cornea 2002;21:173-6.  Back to cited text no. 14
Gahl WA, Kuehl EM, Iwata F, Lindblad A, Kaiser-Kupfer MI Corneal crystals in nephropathic cystinosis: Natural history and treatment with cysteamine eyedrops. Mol Genet Metab 2000;71:100-20.  Back to cited text no. 15
Gahl WA, Reed GF, Thoene JG, Schulman JD, Rizzo WB, Jonas AJ, et al. Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med 1987;316:971-7.  Back to cited text no. 16
Wilmer MJ, Kluijtmans LA, van der Velden TJ, Willems PH, Scheffer PG, Masereeuw R, et al. Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells. Biochim Biophys Acta 2011;1812:643-51.  Back to cited text no. 17
Kalatzis V, Nevo N, Cherqui S, Gasnier B, Antignac C Molecular pathogenesis of cystinosis: Effect of Ctns mutations on the transport activity and subcellular localization of cystinosin. Hum Mol Genet 2004;13:1361-71.  Back to cited text no. 18
Gahl WA, Thoene JG, Schneider JA Cystinosis. N Engl J Med 2002;347:111-21.  Back to cited text no. 19
Bäumner S, Weber LT Nephropathic cystinosis: Symptoms, treatment, and perspectives of a systemic disease. Front Pediatr 2018;6:58.  Back to cited text no. 20
Besouw M, Levtchenko E Growth retardation in children with cystinosis. Minerva Pediatr 2010;62:307-14.  Back to cited text no. 21
Betend B, Chatelain P, David L, François R [Treatment of rickets caused by infantile cystinosis using 1 alpha-hydroxyvitamin D]. Arch Fr Pediatr 1982;39:615-8.  Back to cited text no. 22
Tsilou E, Zhou M, Gahl W, Sieving PC, Chan CC Ophthalmic manifestations and histopathology of infantile nephropathic cystinosis: Report of a case and review of the literature. Surv Ophthal 2007;52:97-105.  Back to cited text no. 23
Chik CL, Friedman A, Merriam GR, Gahl WA Pituitary-testicular function in nephropathic cystinosis. Ann Intern Med 1993;119:568-75.  Back to cited text no. 24
Besouw MT, Kremer JA, Janssen MC, Levtchenko EN Fertility status in male cystinosis patients treated with cysteamine. Fertil Steril 2010;93:1880-3.  Back to cited text no. 25
Reiss RE, Kuwabara T, Smith ML, Gahl WA Successful pregnancy despite placental cystine crystals in a woman with nephropathic cystinosis. N Engl J Med 1988;319:223-6.  Back to cited text no. 26
Robert JJ, Tête MJ, Guest G, Gagnadoux MF, Niaudet P, Broyer M Diabetes mellitus in patients with infantile cystinosis after renal transplantation. Pediatr Nephrol 1999;13:524-9.  Back to cited text no. 27
Ariceta G, Camacho JA, Fernández-Obispo M, Fernández-Polo A, Gamez J, García-Villoria J, et al; Grupo T-CiS.bcn. Cystinosis in adult and adolescent patients: Recommendations for the comprehensive care of cystinosis. Nefrologia 2015;35: 304-21.  Back to cited text no. 28
Trauner DA, Spilkin AM, Williams J, Babchuck L Specific cognitive deficits in young children with cystinosis: Evidence for an early effect of the cystinosin gene on neural function. J Pediatr 2007;151:192-6.  Back to cited text no. 29
Emma F, Nesterova G, Langman C, Labbé A, Cherqui S, Goodyer P, et al. Nephropathic cystinosis: An international consensus document. Nephrol Dial Transplant 2014;29 Suppl 4: iv87-94.  Back to cited text no. 30
Levtchenko E, van den Heuvel L, Emma F, Antignac C Clinical utility gene card for: Cystinosis. Eur J Hum Genet 2014;22. https//doi:10.1038/ejhg.2013.204.  Back to cited text no. 31
Gahl WA Cystinosis. Rare Di sease Database https://rarediseases.org/rare-diseases/cystinosis/ [Last accessed on 3rd June 2022].  Back to cited text no. 32
Van Stralen KJ, Emma F, Jager KJ, Verrina E, Schaefer F, Laube GF, et al. Improvement in the renal prognosis in nephropathic cystinosis. Clin J Am Soc Nephrol 2011;6: 2485-91.  Back to cited text no. 33
Syres K, Harrison F, Tadlock M, Jester JV, Simpson J, Roy S, et al. Successful treatment of the murine model of cystinosis using bone marrow cell transplantation. Blood 2009;114:2542-52.  Back to cited text no. 34
Piotrowska E, Jakóbkiewicz-Banecka J, Barańska S, Tylki-Szymańska A, Czartoryska B, Wegrzyn A, et al. Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses. Eur J Hum Genet 2006;14:846-52.  Back to cited text no. 35
Piotrowska E, Jakóbkiewicz-Banecka J, Tylki-Szymanska A, Liberek A, Maryniak A, Malinowska M, et al. Genistin-rich soy isoflavone extract in substrate reduction therapy for sanfilippo syndrome: An open-label, pilot study in 10 pediatric patients. Curr Ther Res Clin Exp 2008;69:166-79.  Back to cited text no. 36
Haverty T, Wyatt DJ, Porter KM, Leubitz A, Banks K, Goodyer P, et al. Phase i renal impairment trials results supports targeted individual dosing of ELX-02 in patients with nephropathic cystinosis. J Clin Pharma 2021;61:923-31.  Back to cited text no. 37
Phase II clinical trial Cystinosis. Eloxx Pharmaceutical 2021 [Internet]. Available from: https://www.eloxxpharma.com/pipeline/ [Last accessed on 6th April 2022].  Back to cited text no. 38
Stem cell gene therapy 2021(internet). 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT03897361 [Last accessed on 6th April 2022].  Back to cited text no. 39
Emma F, Hoff WV, Hohenfellner K, Topaloglu R, Greco M, Ariceta G, et al. An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis. Kidney Int 2021;100:1112-23.  Back to cited text no. 40
Ivanova EA, van den Heuvel LP, Elmonem MA, De Smedt H, Missiaen L, Pastore A, et al. Altered mtor signalling in nephropathic cystinosis. J Inherit Metab Dis 2016;39:457-64.  Back to cited text no. 41
Wilmer MJ, Christensen EI, van den Heuvel LP, Monnens LA, Levtchenko EN Urinary protein excretion pattern and renal expression of megalin and cubilin in nephropathic cystinosis. Am J Kidney Dis 2008;51:893-903.  Back to cited text no. 42


  [Figure 1]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Clinical Present...
Potential New Tr...
Potential Resear...
Article Figures

 Article Access Statistics
    PDF Downloaded81    
    Comments [Add]    

Recommend this journal