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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
LETTER TO THE EDITOR  
Year : 2013  |  Volume : 24  |  Issue : 1  |  Page : 147-149
Nephropathic cystinosis in a developing country: The Egyptian experience


1 Department of Pediatrics; Center of Pediatric Nephrology and Transplantation, Cairo University; Egyptian Group for Orphan Renal Diseases (EGORD), Cairo, Egypt
2 Department of Pediatrics; Center of Pediatric Nephrology and Transplantation, Cairo University, Cairo, Egypt
3 Department of Pediatrics; Pediatric Endocrinology Unit, Cairo University, Cairo, Egypt

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Date of Web Publication22-Jan-2013
 

How to cite this article:
Soliman NA, Bazaraa HM, Abdel Hamid RH, Badawi N. Nephropathic cystinosis in a developing country: The Egyptian experience. Saudi J Kidney Dis Transpl 2013;24:147-9

How to cite this URL:
Soliman NA, Bazaraa HM, Abdel Hamid RH, Badawi N. Nephropathic cystinosis in a developing country: The Egyptian experience. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2018 Oct 22];24:147-9. Available from: http://www.sjkdt.org/text.asp?2013/24/1/147/106315
To the Editor,

Cystinosis is an autosomal recessive lysosomal storage disorder caused by defects in CTNS, the gene that encodes cystinosin, [1] which is the lysosomal membrane transporter for cystine. Cystine thus accumulates in various tissues. [2] Kidney involvement is the earliest and foremost clinical characteristic, starting with Fanconi's syndrome that generally becomes apparent three to six months after birth. [3] Renal glomerular damage usually appears by two to five years of age, and results in end-stage renal disease (ESRD) before the age of ten years in untreated patients. [4],[5] Other early findings of cystinosis include corneal crystals, poor growth and hypothyroidism, [6] while late complications include various systems. [7]

Successful treatment of nephropathic cystinosis requires early diagnosis. In addition to supportive therapy for tubular dysfunction, specific therapy with cysteamine (b-mercaptoethylamine) [8] has improved the prognosis. Nephropathic cystinosis has been previously described in Egyptian children. [9]

We studied eight children (from seven families; five boys and three girls) with nephropathic cystinosis at our center. Their median age was 7.5 months, with range from four to 14 months. Eighty-eight percent of them (7/8) were the products of consanguineous marriages. Cystinosis was confirmed as the primary diagnosis by slit-lamp examination demonstrating the pathognomonic corneal cystine crystal deposition except for two infants in whom diagnosis was confirmed by high WBC cystine assay as they were both slit-lamp negative for cystine crystals. All the patients received supportive therapy in addition to regular cysteamine for at least 12 months. Children with ESRD requiring renal replacement therapy were excluded from the study. The patients presented with manifestations consistent with proximal tubular dysfunction. The period between the onset of symptoms to starting specific therapy ranged from three to 25 months (median 4.5 months), attributed mostly to delay in the diagnosis of nephropathic cystinosis. Although the average dose of cysteamine was 26.22 mg/kg/day, some of the patients reached up to 30-35 mg/kg/day, and one patient was on 60 mg/kg/ day. Four patients were consistent with CKD stage 1, three with CKD stage 2 and one with CKD stage 3. Other than corneal involvement, no extrarenal manifestations were present. Only one patient had laboratory evidence of hypothyroidism, which was corrected by treatment with levothyroxine. [Figure 1] shows the change in length and weight over the study period. Although the patients still have deviation of their growth parameters from normal, there was partial improvement with a tendency to increase height standard deviation score (median 0.6/year). The annual height gain ranged from 5.4 to 6.9 cm/year, and there was a significant positive correlation between the age of onset of symptoms and annual height. Four patients (50%) had definite e-GFR loss [Figure 2] during the follow-up period, and the median rate of annual e-GFR decline was 3.69 mL/min/1.73 m 2 . At this rate, GFR is expected to reach 10 mL/min/ 1.73 m 2 (consistent with ESRD) at a mean age of 10.7 years in those who had GFR decline. The other four patients did not show e-GFR loss over the follow-up period. From these data, it is projected that 2/8 patients would reach ESRD by ten years of age, consistent with 75% renal survival. At 20 years of age, the projected renal survival would be 50%. There was no significant correlation between annual GFR decline and age of onset or pre-treatment e-GFR. Notably, the patient who received cysteamine at the optimal dosage (60 mg/kg/day) showed an increase from 40 mL/ min/1.73 m² at start of cysteamine therapy to 87.2 mL/min/ 1.73 m² at the end of follow-up. Moreover, he had better increase in height SDS (1.3/year compared with the overall median of 0.6/year).
Figure 1: Change in height and weight standard deviation scores during treatment with cysteamine.

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Figure 2: Correlation between annual height gain and age of onset of symptoms (r = 0.85, P = 0.02).

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Patients had retarded growth at the time of diagnosis as both the median height and the weight SDS for age were less than -2, and this was expected from the results of other studies. [2],[4],[10] During follow-up, our study patients demonstrated partial improvement of height, with a median increase in SDS of 0.6/year whilst adhering to regular cysteamine therapy with out the need for growth hormone . Of interest, we demonstrated that the later the onset of symptoms, the better was the annual height gain, as evidenced by a significant positive correlation (r = 0.85, P = 0.02). In addition, p artially treated patients are expected to lose renal function with time, while early and full treatment hinders such deterioration, as suggested in our study and in others. [7],[10]

It has been previously reported that satisfactory nutrition may be difficult to achieve because of the feeling of satiety that results from the mandatory ingestion of large volumes of fluids and also because of dysgeusia, if cysteamine is being administered. [6]

In addition to the contribution of delayed diagnosis and undertreatment, differences in severity of phenotype may be associated with different CTNS gene mutations, [11] as more than 86 different mutations have been described to date (www.hgmd.cf.ac.uk). Furthermore, a different genetic background, with other gene alleles contributing to overall kidney function and/or differences in the pharmacokinetics and pharmacodynamics of cysteamine, may be implicated. [7] Eight CTNS mutations were identified, four of which were novel (c.530A>G, c.681G>A, 1013T>G and c.1018_1041del) in cystinosis patients of Arab origin. [12]

We emphasize that timely diagnosis and initiation of specific therapy with recommended doses of cysteamine are likely to improve the outcome. Since genetic CTNS mutations may influence phenotype severity and response to therapy, investigative studies into genotype-phenotype correlation in Egyptian children with nephropathic cystinosis are greatly warranted.

 
   References Top

1.Town M, Jean G, Cherqui S, et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet 2004;18:319-24.  Back to cited text no. 1
    
2.Gahl WA, Thoene JG, Schneider JA. Cystinosis: A disorder of lysosomal membrane transport. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic & molecular bases of inherited disease. Vol. 3, 8 th ed. New York: McGraw-Hill; 2001. P. 5085-108.  Back to cited text no. 2
    
3.Geelen JM, Monnens LA, Levtchenko EN. Follow-up and treatment of adults with cystinosis in the Netherlands. Nephrol Dial Transplant 2002;17:1766-70.  Back to cited text no. 3
    
4.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. 4
    
5.Niaudet P, Tełte MJ, Broyer M. Renal disease in cystinosis. In: Broyer M, ed. Cystinosis. Amsterdam: Elsevier; 1999. P. 36-41.  Back to cited text no. 5
    
6.Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med 2002;347:111-21.  Back to cited text no. 6
    
7.Kleta R, Bernardini I, Ueda M, et al. Long term follow-up of well treated nephropathic cystinosis patients. J Pediatr 2004; 145:555-60.  Back to cited text no. 7
    
8.Thoene JG, Oshima RG, Crawhall JC, Olson DL, Schneider JA. Cystinosis. Intracellular ospital depletion by aminothiols in vitro and in vivo. J Clin Invest 1976;58:180-9.  Back to cited text no. 8
    
9.Soliman NA, El-Baroudy R, Risk A, Bazaraa H, Younan A. Nephropathic cystinosis in children: An overlooked disease. Saudi J Kidney Dis Transpl 2009;20:436-42.   Back to cited text no. 9
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10.Markello TC, Bernardini IM, Gahl WA. Improved renal function in children with cystinosis treated with cysteamine. N Engl J Med 1993;328:1157-62.   Back to cited text no. 10
    
11.Attard M, Jean G, Forestier L, et al. Severity of phenotype in cystinosis varies with mutations in the CTNS gene: Predicted effect on the model of cystinosin. Hum Mol Genet 1999;8: 2507-14.  Back to cited text no. 11
    
12.Aldahmesh MA, Humeidan A, Almojalli HA, et al. Characterization of CTNS mutations in Arab patients with cystinosis. Ophthalmic Genet 2009;30:185-9.  Back to cited text no. 12
    

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Correspondence Address:
Neveen A Soliman
Department of Pediatrics; Center of Pediatric Nephrology and Transplantation, Cairo University; Egyptian Group for Orphan Renal Diseases (EGORD), Cairo
Egypt
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DOI: 10.4103/1319-2442.106315

PMID: 23354215

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