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Comparison of clinical and genetic characteristics between Dent disease 1 and Dent disease 2

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Abstract

Background

Dent disease is associated with low molecular weight proteinuria and hypercalciuria and caused by pathogenic variants in either of two genes: CLCN5 (Dent disease 1) and OCRL (Dent disease 2). It is generally not accompanied by extrarenal manifestations and it is difficult to distinguish Dent disease 1 from Dent disease 2 without gene testing. We retrospectively compared the characteristics of these two diseases using one of the largest cohorts to date.

Methods

We performed gene testing for clinically suspected Dent disease, leading to the genetic diagnosis of 85 males: 72 with Dent disease 1 and 13 with Dent disease 2. A retrospective review of the clinical findings and laboratory data obtained from questionnaires submitted in association with the gene testing was conducted for these cases.

Results

The following variables had significantly higher levels in Dent disease 2 than in Dent disease 1: height standard deviation score (height SDS), serum creatinine-based estimated GFR (Cr-eGFR) (median: 84 vs. 127 mL/min/1.73 m2, p < 0.01), serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum lactate dehydrogenase (LDH), serum creatine phosphokinase (CK), serum potassium, serum inorganic phosphorus, serum uric acid, urine protein/creatinine ratio (median: 3.5 vs. 1.6 mg/mg, p < 0.01), and urine calcium/creatinine ratio. There were no significant differences in serum sodium, serum calcium, alkaline phosphatase (ALP), urine β2-microglobulin, incidence of nephrocalcinosis, and prevalence of intellectual disability or autism spectrum disorder.

Conclusions

The clinical and laboratory features of Dent disease 1 and Dent disease 2 were shown in this study. Notably, patients with Dent disease 2 showed kidney dysfunction at a younger age, which should provide a clue for the differential diagnosis of these diseases.

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Funding

This study was supported by Grants-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (subject ID: 19 K17297 to Nana Sakakibara, 17H04189 to Kazumoto Iijima, and 19 K08726 to Kandai Nozu).

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Authors and Affiliations

  1. Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Nana Sakakibara, China Nagano, Shinya Ishiko, Tomoko Horinouchi, Tomohiko Yamamura, Shogo Minamikawa, Shingo Ishimori, Naoya Morisada, Kazumoto Iijima & Kandai Nozu

  2. Department of Pediatrics, Wakayama Medical University, Wakayama, Japan

    Yuko Shima

  3. Department of Pediatrics, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan

    Koichi Nakanishi

  4. Department of Clinical Genetics, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan

    Naoya Morisada

Authors
  1. Nana Sakakibara
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  2. China Nagano
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  3. Shinya Ishiko
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  4. Tomoko Horinouchi
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  5. Tomohiko Yamamura
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  6. Shogo Minamikawa
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  7. Yuko Shima
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  9. Shingo Ishimori
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  10. Naoya Morisada
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  11. Kazumoto Iijima
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  12. Kandai Nozu
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Contributions

NS and KN: study conception and design, interpretation of the data, and drafting of the manuscript. NS: data acquisition and management. All authors: critical revision of the manuscript. All authors gave final approval of the version to be published, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Nana Sakakibara.

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The authors have nothing to disclose.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board of Kobe University Graduate School of Medicine (IRB approval number 301) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individuals participating in this study.

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Sakakibara, N., Nagano, C., Ishiko, S. et al. Comparison of clinical and genetic characteristics between Dent disease 1 and Dent disease 2. Pediatr Nephrol 35, 2319–2326 (2020). https://doi.org/10.1007/s00467-020-04701-5

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  • DOI: https://doi.org/10.1007/s00467-020-04701-5

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