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Dent’s disease: clinical features and molecular basis

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Abstract

Dent’s disease is an X-linked recessive renal tubulopathy characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure. LMWP is the most constant feature, while the other clinical manifestations show wide variability. Patients also present variable manifestations of proximal tubule dysfunctions, such as aminoaciduria, glucosuria, hyperphosphaturia, kaliuresis, and uricosuria, consistent with renal Fanconi syndrome. Dent’s disease affects mainly male children, and female carriers are generally asymptomatic. In two-thirds of patients, the disease is caused by mutations in the CLCN5 gene, which encodes the electrogenic chloride/proton exchanger ClC-5. A few patients have mutations in OCRL1, the gene associated with the oculocerebrorenal syndrome of Lowe, which encodes a phosphatidylinositol-4,5-biphosphate-5-phosphatase (OCRL1). Both ClC-5 and OCRL1 are involved in the endocytic pathway for reabsorption of LMW proteins in the proximal tubule. This review will provide an overview of the important phenotypic characteristics of Dent’s disease and summarize the molecular data that have significantly increased our comprehension of the mechanisms causing this disease.

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Acknowledgments

Funding grants PI09/91009 and PI 17/09 were received from the “Fondo de Investigación Sanitaria” and “Fundación Canaria de Investigación y Salud FUNCIS”, respectively.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Spain

    Félix Claverie-Martín & Elena Ramos-Trujillo

  2. Unidad de Nefrología Pediátrica, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Spain

    Víctor García-Nieto

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  1. Félix Claverie-Martín
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  2. Elena Ramos-Trujillo
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  3. Víctor García-Nieto
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Correspondence to Félix Claverie-Martín.

Additional information

Answers

1.b. Metabolic acidosis could occur when there is advanced chronic kidney disease

2. d.

3. c.

4. c. Increased intestinal absorption of calcium, renal hypercalciuria, and/or increased bone resorption have been reported

5. c.

6. a.

7. a.

8. c.

Questions

Questions

Answers appear following the reference list.

  1. 1.

    Dent’s disease causes a proximal tubulopathy:

    1. a.

      Full (Syndrome de Toni-Debré-Fanconi)

    2. b.

      Incomplete (without metabolic acidosis)

    3. c.

      Isolated (only loss of low-molecular-weight proteins)

    4. d.

      In some cases there is no tubular damage

  2. 2.

    Dent’s disease is caused by mutations:

    1. a.

      In the CLCN5 gene

    2. b.

      In the OCRL1 gene

    3. c.

      In some cases, no causative gene has been found

    4. d.

      All of the above

  3. 3.

    Electrogenic chloride/proton exchanger ClC-5 is expressed in:

    1. a.

      All tubular segments

    2. b.

      Only in the ascending limb of Henle's loop

    3. c.

      Mainly in the proximal tubule

    4. d.

      The glomerulus

  4. 4.

    Hypercalciuria in Dent’s disease is secondary to:

    1. a.

      Proximal tubular damage

    2. b.

      A defect in renal acidification capacity

    3. c.

      There are several possible mechanisms to explain the hypercalciuria; the testing of various hypotheses gives conflicting results

    4. d.

      Hypercalcemia

  5. 5.

    Although there is no specific treatment, what is the best treatment that can be offered to patients with Dent’s disease? :

    1. a.

      Thiazide

    2. b.

      Vitamin D

    3. c.

      Thiazide and drink plenty of fluids

    4. d.

      Citrate salts

  6. 6.

    In which organelle of proximal tubular cells is the electrogenic chloride/proton exchanger ClC-5 expressed?

    1. a.

      Endosomes

    2. b.

      The nucleus

    3. c.

      The Golgi apparatus

    4. d.

      Ribosomes

  7. 7.

    Surprisingly, Dent’s disease can be associated with glomerulopathy:

    1. a.

      Occasionally, it may present as segmental and focal glomerulosclerosis

    2. b.

      Never, it is impossible

    3. c.

      The low-molecular-weight proteinuria is of glomerular origin

    4. d.

      Always

  8. 8.

    OCRL1 gene mutations can cause:

    1. a.

      Syndrome of Lowe

    2. b.

      Dent’s disease

    3. c.

      The previous two

    4. d.

      Neither

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Claverie-Martín, F., Ramos-Trujillo, E. & García-Nieto, V. Dent’s disease: clinical features and molecular basis. Pediatr Nephrol 26, 693–704 (2011). https://doi.org/10.1007/s00467-010-1657-0

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  • DOI: https://doi.org/10.1007/s00467-010-1657-0

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