Kidney Week

Abstract: SA-PO587

Clinical Overview and Long-Term Prognosis of Dent Disease and Lowe Syndrome in Japan

Session Information

• Noncystic Mendelian Diseases
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Genetic Diseases of the Kidney

• 802 Non-Cystic Mendelian Diseases

Authors

• Miura, Ken-ichiro, Tokyo Women's Medical University School of Medicine, Tokyo, Japan, Tokyo, Japan

Ken-ichiro Miura,

• Harita, Yutaka, Department of Pediatrics, University of Tokyo, Tokyo, Japan

Yutaka Harita,

• Ishizuka, Kiyonobu, Tokyo Women's Medical University School of Medicine, Tokyo, Japan, Tokyo, Japan

Kiyonobu Ishizuka,

• Yabuuchi, Tomoo, Tokyo Women's Medical University School of Medicine, Tokyo, Japan, Tokyo, Japan

Tomoo Yabuuchi,

• Kaneko, Naoto, Tokyo Women's Medical University School of Medicine, Tokyo, Japan, Tokyo, Japan

Naoto Kaneko,

• Kanda, Shoichiro, Department of Pediatrics, University of Tokyo, Tokyo, Japan

Shoichiro Kanda,

• Sato, Atsushi, Department of Pediatrics, University of Tokyo, Tokyo, Japan

Atsushi Sato,

• Isojima, Tsuyoshi, Department of Pediatrics, University of Tokyo, Tokyo, Japan

Tsuyoshi Isojima,

• Igarashi, Takashi, National Center for Child Health and Development, Tokyo, Japan

Takashi Igarashi,

• Hattori, Motoshi, Tokyo Women's Medical University School of Medicine, Tokyo, Japan, Tokyo, Japan

Motoshi Hattori,

Background

Epidemiologic data of Dent disease (DD) and Lowe syndrome (LS) are lacking, and long-term prognosis of LS has not been surveyed. The aim of this study was to investigate the prevalence and long-term prognosis of patients with DD and LS in Japan.

Methods

Questionnaire was distributed to 1,814 departments of pediatrics, nephrology, endocrinology and internal medicine of major hospitals in Japan. Data of the patients who visited the hospitals in 3 years (between 2013 and 2015) were collected. This study was approved by the Ethics Committee of Tokyo Women’s Medical University (IRB No.3916) and was supported by Health and Welfare Labour Sciences Research Grants.

Results

The response rate was 49% and 83% in the primary and the secondary survey, respectively. Clinical and laboratory data were obtained from 110 patients with DD and 67 patients with LS. A low response rate and small sample sizes did not allow estimation of patient numbers. The majority of patients with DD were diagnosed asymptomatically by annual urinary screening test at median age of 3 years. Prominent low molecular weight proteinuria (LMWP), hypercalciuria and nephrocalcinosis were noted in 100%, 49% and 37% of patients, respectively. Only 3 (19%) out of 16 adult patients developed CKD stages 3 or 4 in their 20s and 30s. Genetic analyses were performed in 37% and mutations in the CLCN5 and the OCRL genes were documented in 68% and 11%, respectively, the proportion of which was similar to the previous reports. Most patients with LS were diagnosed in infancy. All patients presented with prominent LMWP, cataract and mental retardation. Estimated GFR negatively correlated with age and indicated that most patients developed end stage renal disease in their 30s and 40s. OCRL mutations were documented in 21 (96%) out of 22 patients analyzed.

Conclusion

The prognosis of DD in Japan might be better than that in Europe and USA probably due to detection of individuals with milder phenotypes by annual urinary screening test. It might be suggested that the only required item for the diagnosis of DD is prominent LMWP in Japan. In addition, we described long-term renal prognosis of LS for the first time, which would contribute to treatment strategy and genetic counseling.

Funding

• Government Support - Non-U.S.