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 Table of Contents  
Year : 2021  |  Volume : 6  |  Issue : 2  |  Page : 105-108

Nephropathic infantile cystinosis in an 8-year-old girl: First case report from Bangladesh

1 Department of Pediatric Nephrology, Square Hospitals Ltd, Dhaka, Bangladesh
2 Department of Epidemiology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
3 Department of Ophthalmology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Date of Submission17-Aug-2021
Date of Acceptance15-Dec-2021
Date of Web Publication28-Feb-2022

Correspondence Address:
Dr. M Abdul Qader
Department of Pediatric Nephrology, Square Hospitals Ltd, 18/F, Bir Uttam Qazi Nuruzzaman Sarak, West Panthapath, Dhaka 1205,
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pnjb.pnjb_1_21

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Nephropathic infantile cystinosis is a rare congenital metabolic disorder with an autosomal recessive penetrance in the family, which causes the accumulation of cystine in the lysosomes of different organs of the body. The nephropathic infantile type presents in early infancy in the form of proximal renal tubular acidosis and carries a poor prognosis including renal failure requiring renal replacement therapy and blindness if left untreated. Here we report a case of nephropathic cystinosis in an 8-year-old girl who presented in her early infancy at 8 months of age and was diagnosed as distal renal tubular acidosis and started on alkali therapy. Her symptoms initially improved but she had delayed milestones of motor development, persistent polyuria, and weakness. At the presentation of 8 years, she was found to have features of rickets in both upper and lower limb and hypertensive. Her blood reports revealed a nonanion gap metabolic acidosis with hypokalemia and hypophosphatemia. She also had proteinuria and glycosuria but no hypercalciuria. Considering her clinical and biochemical features, she was sent for eye evaluation, which revealed the presence of cystine crystal in the conjunctiva, stroma of the cornea, and peripheral retina. Clinical diagnosis of cystinosis is often challenging as some cases may mimic features of distal renal tubular acidosis, so careful evaluation is necessary. Parents were counseled about the disease and genetic test and her treatment was continued with phosphate supplement along with alkali supplements. Though the genetic test is confirmatory for diagnosing nephropathic cystinosis, a complete initial evaluation including blood, urine analysis, and an ophthalmological evaluation can guide us toward early diagnosis and management.

Keywords: CTNS gene, nephropathic infantile cystinosis, proximal renal tubular acidosis

How to cite this article:
Qader M A, Patwary M A, Chowdhury T, Choudhury N. Nephropathic infantile cystinosis in an 8-year-old girl: First case report from Bangladesh. Paediatr Nephrol J Bangladesh 2021;6:105-8

How to cite this URL:
Qader M A, Patwary M A, Chowdhury T, Choudhury N. Nephropathic infantile cystinosis in an 8-year-old girl: First case report from Bangladesh. Paediatr Nephrol J Bangladesh [serial online] 2021 [cited 2023 May 30];6:105-8. Available from: http://www.pnjb-online.org/text.asp?2021/6/2/105/338563

  Introduction Top

Cystinosis is a rare metabolic disorder with an autosomal recessive inheritance that results in excessive accumulation of cystine within the lysosomes of different organs of the body.[1] Mutation of the CTNS gene in an individual is responsible for causing cystinosis. CTNS gene encodes a protein, namely cystinosis, which is responsible for the transport of lysosomal cystine. There are three types of presentations of cystinosis, namely infantile nephropathic cystinosis, juvenile nephropathic cystinosis, and non-nephropathic cystinosis or adult-onset cystinosis. Nephropathic infantile cystinosis is the most common form and carries the worst outcome as patients progress to end-stage renal disease (ESRD) in the first decade of life. Juvenile nephropathic cystinosis is rare and is approximately 5% among all the cases of cystinosis. Adult-onset cystinosis presents with photophobia secondary to cystine accumulation in the cornea. The incidence of nephropathic cystinosis is 1 in 100,000 to 200,000 live births in the United States and Europe.[2],[3],[4],[5] Cystinosis is comparatively rare among Asians in comparison to people of the United States and Northern Europe.[6] In this report, we will discuss a case of infantile nephropathic cystinosis who presented at early infancy with features related to proximal renal tubular acidosis and have deposition of cystine crystal in the cornea. We will also discuss the challenges of genetic diagnosis in developing country and management with cysteamine.

  Case Report Top

An 8-year-old girl from a consanguineous parents born at term with a birth weight of 2.6 kg. There was no family history of kidney disease but her two other siblings died in infancy without any diagnosis and she also has two healthy siblings. She presented to a physician at the age of 8 months with growth failure and polyuria. She was investigated and a diagnosis of distal renal tubular acidosis was made at that time and started on Shohl’s solution. She continued with the Shohl’s solution but parents noticed that she had delayed milestones of development, especially motor milestones and persisting polyuria. She was seen in different hospitals but her growth failure did not improve.

At the age of 8 years, she presented to our hospital with problems of growth failure, polyuria, and unable to walk. On examination, she was found to have features of rickets in the form of bowing of both legs, a box-shaped head, widened wrist joint, and a rachitic rosary [Figure 1]. She was also found to be hypertensive with blood pressure 124/85mm Hg, which lies above 95th + 12 mm Hg. Her initial lab evaluation reveals hypokalemia with nonanion gap metabolic acidosis (serum sodium 137 mmol/L, potassium 3.2 mmol/L, chloride 105 mmol/L, bicarbonate 20 mmol/L), hypophosphatemia (serum phosphate 1.9 mg/dL), and hypocalcemia (serum calcium 8.9 mg/dL) with normal serum creatinine (0.46 mg/dL) and normal intact parathyroid level (21.5 pg/mL). Her urine report reveals a pH of 7.5 (as she was already on Shohl’s solution), proteinuria and glycosuria with a normal calcium creatinine ratio and phosphate: creatinine ratio. Ultrasound kidney and bladder revealed increased cortical echogenicity with no evidence of nephrocalcinosis. Considering nonanion gap metabolic acidosis with hypokalemia and hypophosphatemia a diagnosis of proximal renal tubular acidosis was made and the child was sent for ophthalmological evaluation. Slit-lamp examination showed evidence of cystine crystal deposition in both bulbar and palpebral conjunctiva, the stroma of the cornea, and the peripheral retina [Figure 2]. A diagnosis of cystinosis was made and the family was advised for genetic testing to confirm the diagnosis. She was started on a potassium citrate supplement with sodium bicarbonate for correction of acidosis, sodium di-hydrogen phosphate for hypophosphatemia, and enalapril for hypertension. With the aforementioned therapy, her acidosis was corrected and her serum phosphate level normalized and she started to walk after 4 months of therapy [Figure 3].
Figure 1: Bowing of legs in during initial presentation‑

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Figure 2: Evidence of cystine crystals deposition in the conjunctiva, cornea, and fundus of the eye

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Figure 3: Follow-up progression of the girl with growth and biochemical parameters

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  Discussion Top

Diagnosis of infantile nephropathic cystinosis is based on the characteristics of clinical symptoms, presence of renal Fanconi syndrome in the lab reports, corneal cystine crystal deposition, and increased WBC cystine level and confirmed with molecular analysis of the CTNS gene.[1] Patients with nephropathic cystinosis are usually born without any complication and present with the symptoms such as polyuria, polydipsia, growth failure, vomiting, dehydration, and features of rickets and if left untreated, it rapidly progresses to (ESRD in the first decade of life.[6],[7],[8],[9],[10] Cystinosis comprises approximately 5% of the causes of childhood renal failure.[11] Therefore, an early diagnosis is crucial because of early intervention for the depletion of cystine crystals as well as correction of metabolic abnormalities to delay the progression of renal failure and need to start renal replacement therapy.[12]

Deposition of cystine crystal in the cornea leads to photophobia and visual impairment which usually appears in the second decade of life.[13] An ophthalmological evaluation is essential in case of any tubular disorder to ensure an appropriate clinical diagnosis. As there is a limitation of genetic diagnostic tests in developing countries, all the extent of clinical evaluation should be completed before finalizing the diagnosis. Some patients may exhibit features of hypothyroidism or hypogonadism but a good number of them present with features of encephalopathy related to cortical atrophy in the third decade of life.[7],[8],[9],[14] Our patient had the challenge of diagnosing cystinosis as the earlier presentation mimics features of distal renal tubular acidosis. Moreover, an ophthalmological evaluation at an early age might miss the diagnosis of cystinosis as it appears late after renal features.

Patients with nephropathic cystinosis show urinary abnormalities like proteinuria especially low-molecular-weight proteinuria and glycosuria. In other forms of cystinosis, the juvenile form has milder degrees of proteinuria and they progress slowly towards ESRD. In this setting, we are unable to screen for urinary low molecular weight proteinuria so have to rely on generalized proteinuria and other features of cystinosis. Renal biopsy is helpful in the case of differentiating juvenile form of nephropathic cystinosis from infantile form. Findings on renal biopsy might show multinucleated podocytes, deposition of cystine crystals, atrophy of tubules, interstitial fibrosis, and glomerular solidification. Among them, multinucleated tubulopathy is the hallmark of nephropathic cystinosis.[15]

A genetic diagnosis is a powerful tool for diagnosing nephropathic cystinosis. The cystinosis gene, CTNS, is located on the short arm of chromosome 17 (locus 17p13) which encodes a lysosomal transmembrane protein cystinosin responsible for transfer of cystine from lysosomes to the cytoplasm.[7],[16],[17],[18] As in Bangladesh, genetic testing for diagnosing the rare disease is still under research level in few laboratories but widely done commercially from overseas institutes. Therefore, the cost of the test is always an important issue for economically struggling families. Molecular analysis of CTNS genes can be used for early diagnosis such as prenatal diagnosis in suspected pregnancy. Patients with infantile nephropathic cystinosis usually have either deletion or other mutations causing a complete absence of the protein cystinosin.

Differential diagnosis of cystinosis includes other hereditary causes of Fanconi syndrome such as oculocerebral syndrome (Lowe syndrome), Fanconi-Bickel syndrome, Dent’s disease, tyrosinemia, Wilson’s disease, Galactosemia, Hereditary fructose intolerance, Type-I glycogenosis, metachromatic leukodystrophy, and mitochondrial disease. In our case a patient presents with typical clinical features of proximal renal tubular acidosis with the presence of cystine crystal in the slit lamp examination excludes other differentials. Genetic diagnosis should be established before starting therapy with cysteamine and a white cell cystine level is always an important tool for monitoring clinical parameters. In our case, the financial burden makes both the genetic diagnosis and treatment with cysteamine difficult.

  Conclusion Top

The initial presentation of cystinosis may mimic a picture of distal renal tubular acidosis. The presence of proteinuria with glycosuria can be a hint to think about proximal renal tubular disorder. A slit-lamp examination can help to confirm the diagnosis of cystinosis without a genetic test. But without specific treatment with cysteamine, the long-term prognosis cannot be prevented.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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:iv87-94.  Back to cited text no. 1
Nesterova G, Gahl W Nephropathic cystinosis: Late complications of a multisystemic disease. Pediatr Nephrol 2008;23:863-78.  Back to cited text no. 2
Hult M, Darin N, von Döbeln U, Månsson JE Epidemiology of lysosomal storage diseases in Sweden. Acta Paediatr 2014;103: 1258-63.  Back to cited text no. 3
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. 4
North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS).NAPRTCS annual reports. NAPRTCS Online. 2011. Available from: https://web.emmes.com/ study/ped/annlrept/annlrept.html  Back to cited text no. 5
Soliman NA, Elmonem MA, van den Heuvel L, Abdel Hamid RH, Gamal M, Bongaers I, et al. Mutational spectrum of the CTNS gene in Egyptian patients with nephropathic cystinosis. JIMD Rep2014;14:87-97.  Back to cited text no. 6
Gahl WA, Thoene JG, Schneider JA Cystinosis. N Engl J Med 2002;347:111-21.  Back to cited text no. 7
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.  Back to cited text no. 8
Nesterova G, Gahl WA Cystinosis: The evolution of a treatable disease. Pediatr Nephrol 2013;28:51-9.  Back to cited text no. 9
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. 10
Middleton R, Bradbury M, Webb N, O’Donoghue D, Van’t Hoff W Cystinosis. A clinicopathological conference. “From toddlers to twenties and beyond” adult-paediatric nephrology interface meeting, Manchester 2001. Nephrol Dial Transplant 2003;18:2492-5.  Back to cited text no. 11
Prencipe G, Caiello I, Cherqui S, Whisenant T, Petrini S, Emma F, et al. Inflamose activation by cystine crystals: Implications for the pathogenesis of cystinosis. J Am Soc Nephrol 2014;25:1163-9.  Back to cited text no. 12
Bäumner S, Weber LT Nephropathic cystinosis: Symptoms, treatment, and perspectives of a systemic disease. Front Pediatr 2018;6:58.  Back to cited text no. 13
Lucky AW, Howley PM, Megyesi K, Spielberg SP, Schulman JD Endocrine studies in cystinosis: Compensated primary hypothyroidism. J Pediatr 1977;91:204-10.  Back to cited text no. 14
Chandra M, Stokes MB, Kaskel F Multinucleated podocytes: A diagnostic clue to cystinosis. Kidney Int 2010;78:1052.  Back to cited text no. 15
Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet 1998;18:319-24.  Back to cited text no. 16
The Cystinosis Collaborative Research Group. Linkage of the gene for cystinosis to markers on the short arm of chromosome 17. Nat Genet 1995;10:246-8.  Back to cited text no. 17
Kalatzis V, Cherqui S, Antignac C, Gasnier B Cystinosin, the protein defective in cystinosis, is a H(+)-driven lysosomal cystine transporter. Embo J 2001;20:5940-9.  Back to cited text no. 18


  [Figure 1], [Figure 2], [Figure 3]


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