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Cystinosis: the evolution of a treatable disease

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Abstract

Cystinosis is a rare autosomal recessive disorder involving lysosomal storage of the amino acid cystine due to a defect in the membrane transport protein, cystinosin. Since the introduction of kidney transplants and the availability of cystine-depleting medical therapy, this previously fatal disease was transformed into a treatable disorder. Renal allografts and medical therapy targeting the basic metabolic defect have altered the natural hisotry of cystinosis so drastically that patients have a life expectancy extending past 50 years. Consequently, early diagnosis and appropriate therapy are critically important. In this article, we offer a review of the manifestations of cystinosis, including the proximal tubular dysfunction of renal Fanconi syndrome, and discuss the prevention and treatment of the disorder’s systemic complications. We focus on the nephropathic forms of cystinosis, aiming to assist nephrologists and other physicians to develop early recognition and appropriate management of cystinosis patients.

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Authors and Affiliations

  1. NHGRI, Medical Biochemical Genetic Section, National Institutes of Health, Bethesda, MD, USA

    Galina Nesterova & William A. Gahl

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  1. Galina Nesterova
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  2. William A. Gahl
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Correspondence to Galina Nesterova.

Additional information

Answers:

1)4.

2)4.

3)3.

4)3

5)2.

6)2.

Multiple choice questions: answers are provided following the reference list

Multiple choice questions: answers are provided following the reference list

  1. 1)

    Possible mechanisms for the renal injury of cystinosis include:

    1. 1.

      Renal tissue sensitivity to cystine accumulation

    2. 2.

      Expression of different splice isoforms of CTNS in the kidney

    3. 3.

      High sensitivity of the proximal tubule to apoptosis and energy depletion

    4. 4.

      All of the above

  2. 2)

    The most frequent cause of renal Fanconi syndrome in children is:

    1. 1.

      Renal transplant rejection

    2. 2.

      Heavy metal poisoning, i.e. lead

    3. 3.

      Oculocerebrorenal syndrome of Lowe

    4. 4.

      Cystinosis

    5. 5.

      Mitochondrial cytopathies

  3. 3)

    Which is not a common complication of NC in the first decade of life?

    1. 1.

      Corneal clouding due to cystine crystal accumulation

    2. 2.

      Hypothyroidism

    3. 3.

      Diabetes mellitus

    4. 4.

      Growth failure

    5. 5.

      Hypophosphatemic rickets

  4. 4)

    What percent of all childhood ESRD is contributed by NC:

    1. 1.

      About 10 %

    2. 2.

      Based on the longitudinal multi center studies, 5-10 %

    3. 3.

      Based on European Collaborative study, about 5 %

    4. 4.

      Close to 0 %

  5. 5)

    Normal values for leucocyte cystine content are:

    1. 1.

      Less than 1 nmol/half cystine/mg cell protein

    2. 2.

      Less than 0.2 nmol/half cystine/mg cell protein

    3. 3.

      No higher than 2 nmol/half cystine/mg cell protein

    4. 4.

      Non- detectable

  6. 6)

    The mechanism of action of cysteamine in targeting the basic defect in cystinosis involves:

    1. 1.

      Depleting cells by carrying cystine out of the cell into extracellular space

    2. 2.

      Interacting with cystine and forming cystine-cysteamine disulfide, and exporting this molecule from lysosome into cytosol

    3. 3.

      Restoring normal cystinosin function

    4. 4.

      Protecting cells from apoptosis

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Nesterova, G., Gahl, W.A. Cystinosis: the evolution of a treatable disease. Pediatr Nephrol 28, 51–59 (2013). https://doi.org/10.1007/s00467-012-2242-5

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