Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지

A Case of Congenital Nephrogenic Diabetes Insipidus Confirmed by Gene Analysis

유전자 분석검사로 확진된 선천성 신성 요붕증 1례

  • Cho, Eun Young (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Oh, Jin Hee (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Koh, Dae Kyun (Department of Pediatrics, College of Medicine, The Catholic University of Korea)
  • 조은영 (가톨릭대학교 의과대학 소아과학교실) ;
  • 오진희 (가톨릭대학교 의과대학 소아과학교실) ;
  • 고대균 (가톨릭대학교 의과대학 소아과학교실)
  • Received : 2005.01.04
  • Accepted : 2005.03.07
  • Published : 2005.06.15
Download PDF
⟨ Previous Next ⟩

Abstract

Nephrogenic diabetes insipidus (NDI) is a disorder in which the secretion of antidiuretic hormone is normal, but the response of the renal collecting tubules to vasopressin is impaired. Compared with acquired NDI (a-NDI), which is secondary to chronic bilateral incomplete urinary tract obstruction with hydronephrosis, congenital NDI (c-NDI) is a very rare heritable disorder that usually follows the X- linked recessive pattern. Clinical symptoms of c-NDI can be non specific, and often the disease ultimately results in failure to thrive, or mental retardation. Recently, the diagnosis can be confirmed by direct sequencing analysis of the peripheral blood specimens. The long-term results of treatment for c-NDI are not satisfactory. Reports on the follow up of c-NDI cases are rare and there is no report on the cases treated with combinations of three drugs. We report herein a case of severe c-NDI in an 8 year-old-boy with a severely dysconfigurated urinary tract system. The patient and his mother showed a frameshift mutation on the AVPR2 gene on chromosome Xq28:.847_851delTGCTG (p.C283fsX90). The patient showed normal growth and development by treatment with combinations of hydrochlorothiazide ($65mg/m^2$), amiloride (0.3 mg/kg/d) and indomethacin ($100mg/m^2$), yet after five years he needed adjuvant cystostomy to relieve him from the residual symptoms of urgency with polyuria.

신성 요붕증은 항이뇨호르몬의 정상적 분비에도 불구하고, 신장의 집합관의 항이뇨호르몬에 대한 반응이 저하되어 요농축능에 이상이 초래되는 질환이다. 특히 선천성 신성 요붕증은 대게 반성 열성 유전 양식을 따르는 유전 질환으로 매우 드물어 소아에서는 간헐적 보고만 있어 왔다. 어린 소아에서는 증상이 비특이적일 수 있고, 임상적 진단도 쉽지 않은데, 최근에는 항이뇨 호르몬 수용체 유전자의 돌연변이들이 확인되어 유전자 검사로 확진이 가능하게 되었다. 기존의 보고들은 선천성 신성 요붕증이 진단된 환아들에 대한 이뇨제나 비스테로이드성 항염증제 등을 포함한 치료가 이루어진 증례보고이었으나 이들의 치료 후 장기적 추적 결과 보고가 극히 드물며, 이들 약제에 의한 치료 효과는 낮은 것으로 알려져 있다. 저자들은 극심한 이뇨로 인한 이차적 요로기관의 변형이 초래되었던 8세 소아에서 환아와 엄마의 말초 혈액 유전자 분석 검사상 Xq28 염색체 부위의 AVPR2 유전자의 돌연변이가 확인되었고 hydrochlorothiazide, indomethacin 및 amiloride 병합 치료 후 배뇨량은 하루 12리터에서 4리터로 감소하였고, 성장 발육도 정상이었으나 더 이상의 호전이 없고 일상 생활에 불편함이 지속되어 보조적 방광루 형성술을 시행받은 후, 증상 호전 및 심리적 안정을 얻었던 심한 선천성 신성 요붕증 1례의 5년간의 추적 관찰 결과를 보고하는 바이다.

Keywords

References

  1. Benchimol C. Nephrogenic diabetes insipidus. Pediatr Rev 1996;17:145-6 https://doi.org/10.1542/pir.17-4-145
  2. Forssman H. On hereditary diabetes insipidus with regard to a sex-linked form. Acta Med Scand 1945;159:3-196
  3. Sohn YM, Lee C, Kim PK, Yun DJ. A case of congenital nephrogenic diabetes insipidus with bilateral hydronephrosis. J Korean Pediatr Soc 1980;23:417-21
  4. Suh WB, Jeon JY, Cha SH, Cho BS, Ahn CI. A case of Nephrogenic diabetes insipidus with vesicoureteral reflux. J Korean Pediatr Soc 1991;34:1299-304
  5. Knoers N, van der Heyden H, van Oost BA, Ropers HH, Monnens LA, Willems J. Nephrogenic diabetes insipidus :Close linkage with markers from distal long arm of the human X-chromosome. Hum Genet 1998;80:31-8 https://doi.org/10.1007/BF00451451
  6. Park HW, Park JD, Kim HS, Kim HJ, Lee YK, Ha IS, et al. Analysis of vasopressin receptor type 2(AVPR2) gene in a pedigree with congenital nephrogenic diabetes insipidus : Identification of a family with R202C Mutation in AVPR2 gene. J Korean Soc Pediatr Nephrol 1999;3:209-16
  7. Cheong HI, Park HW, Ha IS, Moon HN, Choi Y, Ko KW, et al. Six novel mutations in the vasopressin V2 receptor gene causing nephrogenic diabetes insipidus. Nephron 1997; 75:431-7 https://doi.org/10.1159/000189581
  8. Hochberg Z, Lieburg AV, Even L, Brenner B, Lanir N, van Oost BA, et al. Autosomal recessive nephrogenic diabetes insipidus caused by an aquaporin-2 mutation. J Clin Endocrinol Metab 1997;82:686-9 https://doi.org/10.1210/jc.82.2.686
  9. Canfield MC, Tamarappoo BK, Moses AM, Verkman AS, Holtzman EJ. Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopression response. Hum Mol Genet 1997;6:1865-71 https://doi.org/10.1093/hmg/6.11.1865
  10. Bichet DG. Nephrogenic diabetes insipidus. Am J Med 1998;105:431-42 https://doi.org/10.1016/S0002-9343(98)00301-5
  11. Chang YI, Kim HU, Kim HD, Shin YS, Lee JM, Kim HS, et al. A case of congenital nephrogenic diabetes insipidus with bilateral hydronephrosis and hydroureter. Korean J Nephrol 2002;21:1026-31
  12. Bendz H, Aurell M. Drug-induced diabetes insipidus. Drug Saf 1999;21:449-56 https://doi.org/10.2165/00002018-199921060-00002
  13. Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, Goodyer P, et al. Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus. Am J Hum Genet 1994;55:278-86
  14. Deen PM, Verdijk MA, Knoers NV, Wieringa B, Monnens LA, van Os CH, et al. Requirement of human renal water chanel aquaporin-2 for vassopressin-dependent concentration of urine. Science 1994;264:92-5 https://doi.org/10.1126/science.8140421
  15. Cheetham T, Baylis PH. Diabetes insipidus in children :pathophysiology, diagnosis and management. Paediatr Drugs 2002;4:785-96
  16. Knoers N, Monnens LA. Nephrogenic diabetes insipidus :clinical symptoms, pathogenesis, genetics and treatment. Pediatr Nephrol 1992;6:476-82 https://doi.org/10.1007/BF00874020
  17. Nijenhuis M, Akker VD, Zalm R. Familial neurohypophysial diabetes insipidus in a large Dutch kindred: effect of the onset of diabetes on growth in children and cell biological defects of the mutant vasopressin prohormone. J Clin Endocrinol Metab 2001;86:3410-20 https://doi.org/10.1210/jc.86.7.3410
  18. Lieburg AF, Knoers NV, Monnens LA. Clinical presentation and follow-up of 30 patients with congenital nephrogenic diabetes insipidus. J Am Soc Nephrol 1999;10:1958-64
  19. Richman RA, Post EM, Notman DD, Hochberg Z, Moses AM. Simplifying the diagnosis of diabetes insipidus in children. Am J Dis Child 1981;135:839-41
  20. Cheetham T, Baylis PH. Diabetes insipidus in children pathophysiology, diagnosis and management. Pediatr Drugs 2002;4:785-96
  21. Bonioli E, Bellini C. Therapy for hereditary nephrogenic diabetes insipidus. J pediatr 1991;119:331 https://doi.org/10.1016/S0022-3476(05)80760-7
  22. Kirchlechner V, Koller DY, Seidl R, Waldhauser F. Treatment of nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride. Arch Dis Child 1999;80:548-52 https://doi.org/10.1136/adc.80.6.548
  23. Uyeki TM, Barry FL, Rosenthal SM, Mathias RS. Successful treatment with hydrochlorothizide and amiloride in an infant with congenital nephrogenic diabetes insipidus. Pediatr Nephrol 1993;7:554-6 https://doi.org/10.1007/BF00852546
  24. Knoers N, Monnerns LA. Amiloride-hydrochlorothiazide versus indomethacin-hydrochlorothiazide in the treatment of nephrogenic diabetes insipidus. J Pediatr 1990;117:499-502 https://doi.org/10.1016/S0022-3476(05)81106-0
  25. Lim SD, Park KW, Rim HK, Kim JS, Rim JS. A case of nephrogenic diabetes insipidus complicated with bilateral hydroureteronephrosis and myogenic failure of bladder. Korean J Nephrol 2000;41:685-8