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Journal of Endocrinological Investigation

, Volume 29, Issue 10, pp 928–933 | Cite as

Gene analysis of the calcium channel 1 subunit and clinical studies for two patients with hypokalemic periodic paralysis

  • K. Kageyama
  • K. Terui
  • S. Tsutaya
  • E. Matsuda
  • M. Shoji
  • S. Sakihara
  • T. Nigawara
  • S. Takayasu
  • T. Moriyama
  • M. Yasujima
  • T. Suda
Case Report

Abstract

Hypokalemic periodic paralysis (HypoPP) is a skeletal muscle disorder in which episodic attacks of muscle weakness occur; they are associated with decreased serum potassium (K+) levels. Recent molecular approaches have clarified that the condition is caused by mutations in the skeletal muscle voltage-gated calcium channel 1 subunit (CACNA 1S). We describe two unrelated patients with HypoPP, followed by their relevant clinical studies and gene analysis. Clinical studies included an oral glucose tolerance test (OGTT), food-loading and insulin tolerance tests (ITT). For Case 1, serum K+ levels were extremely decreased following insulin tolerance testing compared with levels for controls. These results support the hypothesis that no efflux of K+ ion occurs in patients because of low activity of adenosine triphosphate (ATP)-sensitive K+ channel (KATP) channels. Mutational analysis of the CACNA 1S gene showed a duplicate insertion of 14 base pairs (bp) from 52 to 65 in intron 26, present in the heterozygous state in both patients. No other mutations were detected in the CACNA 1S gene, the muscle sodium channel gene (SCN 4A) or the voltage-gated K+ channel gene (KCN3) of either patient. Further analysis showed that this duplicate insertion of 14 bp in intron 26 of the CACNA 1S gene was found in 23.7% of healthy subjects. K+ dynamics studies are useful for confirming this syndrome, while further gene analysis for various ion channels using amplification and direct sequencing are required to evaluate the molecular basis of the disorder in the individual patient.

Key-words

Hypokalemia calcium channel periodic paralysis gene mutation 

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Copyright information

© Italian Society of Endocrinology (SIE) 2006

Authors and Affiliations

  • K. Kageyama
    • 1
  • K. Terui
    • 1
  • S. Tsutaya
    • 2
  • E. Matsuda
    • 2
  • M. Shoji
    • 3
  • S. Sakihara
    • 1
  • T. Nigawara
    • 1
  • S. Takayasu
    • 1
  • T. Moriyama
    • 1
  • M. Yasujima
    • 3
  • T. Suda
    • 1
  1. 1.Department of Endocrinology, Metabolism and Infectious DiseasesHirosaki University School of MedicineJapan
  2. 2.Department of Clinical LaboratoryHirosaki University HospitalJapan
  3. 3.Department of Laboratory MedicineHirosaki University School of MedicineAomoriJapan

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