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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2017  |  Volume : 28  |  Issue : 5  |  Page : 1180-1183
Infantile cystinosis: From dialysis to renal transplantation


1 Department of Pediatric Nephrology, Charles Nicolle Hospital, Tunis, Tunisia
2 Department of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia

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Date of Web Publication21-Sep-2017
 

   Abstract 


Cystinosis is an autosomal recessive, lysosomal storage disease characterised by the accumulation of the amino acid cystine in different organs and tissues. It is a multisystemic disease that can present with renal and extra-renal manifestations. In this report, we present the first case of transplanted nephropathic cystinosis in a Tunisian child. A 4-year-old Tunisian boy born to nonconsanguineous parents, was treated in our medical services in 1990 for cystinosis. Since the age of five months, he developed symptoms of severe weight loss, vomiting, dehydration, and polyuria. He manifested the Toni Debré Fanconi syndrome. Slit lamp examination of the anterior segment of both eyes revealed fine, shiny crystal-like deposits diffusely distributed in the corneal epithelium and the stroma. Our patient had renal failure. At the age of seven, he reached terminal chronic renal failure and was treated with peritoneal dialysis. Hemodialysis was started at the age of nine years. At the age of 13 years, he received a renal transplantation and was started on cysteamine 1999, five months after the renal transplantation. Currently, the patient is 28-year-old. The graft has survived 15 years after the transplantation. Renal functions were stable with a serum creatinine of 123 μmol/L at last follow-up.

How to cite this article:
Jellouli M, Ferjani M, Abidi K, Zarrouk C, Abdelmoula J, Gargah T. Infantile cystinosis: From dialysis to renal transplantation. Saudi J Kidney Dis Transpl 2017;28:1180-3

How to cite this URL:
Jellouli M, Ferjani M, Abidi K, Zarrouk C, Abdelmoula J, Gargah T. Infantile cystinosis: From dialysis to renal transplantation. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2020 Aug 12];28:1180-3. Available from: http://www.sjkdt.org/text.asp?2017/28/5/1180/215119



   Introduction Top


Cystinosis is a lysosomal storage disease that is inherited in an autosomal recessiving manner, and is characterized by the accumulation of cystine in the lysozymes of all the tissues which leads to organ dysfunction, more particularly in the kidneys.[1],[2],[3] It is a clinically heterogeneous disorder that has been divided into three allelic forms based on the age of occurrence and the extent of kidney disease. The early occurring and most common form of cystinosis is the infantile form which is also called nephropathic cystinosis, and is characterized by severe proximal tubular dysfunction; the juvenile form is the intermediate form both in its severity and age of occurrence of cystinosis; the ocular form is often asymptomatic.[4] These three forms are due to CNTS gene mutations. At least, 80 mutations have been reported so far.[5] The introduction of the cysteamine in the 1980’s completely changed the prognosis of cystinosis, allowing to slowing down the progression of the disease to end-stage renal disease (ESRD), to limit the growth disorders and to delay or even prevent the development of extra-renal complications.[6],[7],[8],[9] Nevertheless, in developing countries, the diagnosis is often made at a late stage because of the lack or nonavailability of diagnostic tools and thus results in delayed treatment. Renal transplantation has transformed cystinosis from a fatal pediatric disease into a treatable one, with which patients can survive into adulthood. We report an infantile cystinosis treated with renal transplantation.


   Case Report Top


H. A., a 4-year-old Tunisian boy born to nonconsanguineous parents, was treated in our medical services in 1990 for cystinosis. His family history was significant with two sisters having died at the age of five and 13 months with clinical signs of dehydration and polyuria. The patient showed, since the age of five months, severe weight loss, vomiting, dehydration, polyuria and had been repeatedly admitted and treated for dehydration. He was admitted to our medical services at the age of four years. On examination, his height and weight were below the 3rd centile and he did not have any dysmorphic features. He had wide wrists, rachitic rosary, double malleoli and genu valgum, and polyuria at 6 mL/kg/h. The abdomen was protuberant without organomegaly. The cardiovascular and respiratory examinations were normal. After blood analysis and urinalysis, we concluded that he had a Toni Debré Fanconi syndrome. Slit lamp examination of the anterior segment of both eyes revealed fine, shiny, crystal-like deposits diffusely distributed in the corneal epithelium and stroma. At the age of nine years, he had hypothyroidism and required thyroid hormone treatment. Additionally, our patient had renal failure with a creatinine clearance of 44 mL/min. At the age of seven years, he reached ESRD and was treated initially with peritoneal dialysis. Subsequently, hemodialysis was started at the age of nine years. At the age of 13 years, he received a renal transplantation from a cadaveric donor. He presented with cytomegalovirus infection three months after transplantation as well as noninsulin dependent diabetes mellitus. Renal graft biopsy was performed due to transient failure of renal function, which showed mild fibrosis and excluded signs of rejection. The patient was treated with cysteamine in 1999, five months after the renal transplantation. Currently, the patient is 28-year-old. The graft has survived 15 years after the transplantation. Renal functions are stable with a serum creatinine rate of 123 μmol/L. No extra-renal complications were noted.


   Discussion Top


To our knowledge, this is the first case of renal transplantation for infantile cystinosis in our country with a favorable outcome and graft survival at 15 years. Cystinosis is an autosomal recessive disease. It is quite rare in our country despite the high rate of consanguinity. It might be under-diagnosed due to the lack of diagnosis facilities in our country. Indeed, the white blood cell cystine assay was the test of choice to confirm the diagnosis of cystinosis, monitoring response to treatment and dose adjustment. Currently, genetic testing by mutation analysis of the CTNS gene is a better alternative to confirm the diagnosis. These two tests are not available in our country, are highly costly and technically difficult to perform; there are only a few laboratories worldwide that can perform the test. This explains the delay in diagnosis in our patient. In fact, the diagnosis of nephropathic cystinosis in this case was obtained at the age of four years and was based on the family’s medical history, the presence of corneal cystine crystals in an infant with Fanconi syndrome.

The first symptoms developed from the age of five to six months including anorexia, vomiting, polyurodipsia, and failure to thrive with important deviation of growth parameters from normal, associated with a Fanconi syndrome which is the most common renal manifestation characterized by proximal tubu-lopathy (glycosuria, tubular proteinuria, loss of bicarbonate, potassium, phosphorus, etc.).[10] This was the situation in our patient who presented at the age of five months with classical clinical symptoms of a Fanconi syndrome with polyuria. Cases of rickets have been described and attributed to renal loss of calcium, phosphate and hypophosphatemia.[11] The other manifestations of nephropathic cystinosis are extra-renal and are developed at a later stage of the disease. These include myopathy and dysphagia due to the accumulation of cystine in the muscles, endocrine involvement such as hypothyroidism and diabetes mellitus, hepatomegaly, hypersplenism and photophobia from the accumulation of cystine in the cornea. Fundoscopy may show depigmentation of the retina. Retinal changes may appear before the corneal features.[12] Among these events, our patient had ocular involvement and hypothyroidism. Treatment by cysteamine has dramatically changed the prognosis of cystinosis. If started early, this treatment allows us to delay, and possibly prevent the spontaneous evolution towards ESRD between six and 12 years of age and to avoid growth failure.[13],[14],[15] The initiation of specific therapy with recommended doses of cysteamine at the age of 15 days can even prevent the appearance of tubular signs.[16] Our patient started the specific treatment five years after transplantation and as soon as the medication was available in our country. After renal transplantation, there was no risk of recurrence of tubulopathy since it is a cell disease that does not depend on the circulating factor. If cystine crystals are found in the graft, they depend on the immune cells of the host. However, treatment with cysteamine must be continued to delay or even prevent the occurrence of extra-renal complications. Results following transplantation in these cases in terms of graft survival have been reported to be much better than those of patients with other renal diseases.[17]


   Conclusion Top


We emphasize the importance of pursuing the treatment with cysteamine for patients after renal transplantation to delay the occurrence of extra-renal complications.

Conflict of interest: None declared.



 
   References Top

1.
Drube J, Schiffer E, Mischak H, et al. Urinary proteome pattern in children with renal Fanconi syndrome. Nephrol Dial Transplant 2009;24:2161-9.  Back to cited text no. 1
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2.
Nesterova G, Gahl W. Nephropathic cystinosis: Late complications of a multisystemic disease. Pediatr Nephrol 2008;23:863-78.  Back to cited text no. 2
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3.
Thoene J, Lemons R, Anikster Y, et al. Mutations of CTNS causing intermediate cystinosis. Mol Genet Metab 1999;67:283-93.  Back to cited text no. 3
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4.
Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med 2002;347:111-21.  Back to cited text no. 4
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5.
Soliman NA, Elmonem MA, van den Heuvel L, et al. Mutational spectrum of the CTNS gene in Egyptian patients with nephropathic cystinosis. JIMD Rep 2014;14:87-97.  Back to cited text no. 5
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6.
Ivanova E, De Leo MG, De Matteis MA, Levtchenko E. Cystinosis: Clinical presentation, pathogenesis and treatment. Pediatr Endocrinol Rev 2014;12 Suppl 1:176-84.  Back to cited text no. 6
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7.
Pache de Faria Guimaraes L, Seguro AC, Shimizu MH, et al. N-acetyl-cysteine is associated to renal function improvement in patients with nephropathic cystinosis. Pediatr Nephrol 2014;29:1097-102.  Back to cited text no. 7
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8.
Theodoropoulos DS, Krasnewich D, Kaiser-Kupfer MI, Gahl WA. Classic nephropathic cystinosis as an adult disease. JAMA 1993; 270:2200-4.  Back to cited text no. 8
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9.
Broyer M. Cystinosis. In: Inborn Metabolic Diseases, 4th edn. J Fernandez, JM Saudubray, G van den Berghe, JH Walter (eds). Springer Medizin Verlag, Heidelberg, 2006. p. 531-8.  Back to cited text no. 9
    
10.
Al-Haggar M. Cystinosis as a lysosomal storage disease with multiple mutant alleles: Phenotypic-genotypic correlations. World J Nephrol 2013;2:94-102.  Back to cited text no. 10
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11.
Brodin-Sartorius A, Tête MJ, Niaudet P, et al. Cysteamine therapy delays the progression of nephropathic cystinosis in late adolescents and adults. Kidney Int 2012;81:179-89.  Back to cited text no. 11
    
12.
Emma F, Nesterova G, Langman C, et al. Nephropathic cystinosis: An international consensus document. Nephrol Dial Transplant 2014;29 Suppl 4:iv87-94.  Back to cited text no. 12
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13.
Cherqui S. Cysteamine therapy: A treatment for cystinosis, not a cure. Kidney Int 2012;81:127-9.  Back to cited text no. 13
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14.
Gultekingil Keser A, Topaloglu R, Bilginer Y, Besbas N. Long-term endocrinologic complications of cystinosis. Minerva Pediatr 2014; 66:123-30.  Back to cited text no. 14
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15.
Gahl WA, Balog JZ, Kleta R. Nephropathic cystinosis in adults: Natural history and effects of oral cysteamine therapy. Ann Intern Med 2007;147:242-50.  Back to cited text no. 15
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16.
Ariceta G, Lara E, Camacho JA, et al. Cysteamine (Cystagon®) adherence in patients with cystinosis in Spain: Successful in children and a challenge in adolescents and adults. Nephrol Dial Transplant 2015;30:475-80.  Back to cited text no. 16
    
17.
Spicer RA, Clayton PA, McTaggart SJ, Zhang GY, Alexander SI. Patient and graft survival following kidney transplantation in recipients with cystinosis: A cohort study. Am J Kidney Dis 2015;65:172-3.  Back to cited text no. 17
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Correspondence Address:
Manel Jellouli
Department of Pediatric Nephrology, Charles Nicolle Hospital, Tunis 1007
Tunisia
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PMID: 28937083

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    Abstract
   Introduction
   Case Report
   Discussion
   Conclusion
    References
 

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