Severe Osteomalacia with Dent Disease Caused by a Novel Intronic Mutation of the CLCN5 gene

Intern Med. 2018 Dec 15;57(24):3603-3610. doi: 10.2169/internalmedicine.1272-18. Epub 2018 Aug 10.

Abstract

We present a case of Dent disease caused by a novel intronic mutation, 1348-1G>A, of the chloride voltage-gated channel 5 (CLCN5) gene. Cultured proximal tubule cells obtained from the patient showed impaired acidification of the endosome and/or lysosome, indicating that the 1348-1G>A mutation was indeed the cause of Dent disease. Although the prevalence of osteomalacia in Dent disease is low in Japan, several factors-including poor medication adherence-caused severe osteomalacia in the current case. Oral supplementation with calcium and native/active vitamin D therapy, with careful attention to medication adherence, led to the improvement of the patient's bone status.

Keywords: CLCN5; Dent disease; intronic mutation; osteomalacia.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Calcium, Dietary / therapeutic use
  • Chloride Channels / genetics*
  • Dent Disease / complications
  • Dent Disease / genetics*
  • Dent Disease / pathology
  • Dietary Supplements
  • Humans
  • Introns
  • Japan
  • Kidney Tubules, Proximal / pathology
  • Male
  • Medication Adherence
  • Osteomalacia / drug therapy
  • Osteomalacia / etiology
  • Osteomalacia / genetics*
  • Osteomalacia / pathology
  • Point Mutation*
  • Vitamin D / therapeutic use
  • Vitamins / therapeutic use

Substances

  • CLC-5 chloride channel
  • Calcium, Dietary
  • Chloride Channels
  • Vitamins
  • Vitamin D