Abstract
Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder, mostly caused by AVPR2 mutations. Less than 10% of cases are due to mutations in the aquaporin-2 (AQP2) gene. Diagnosis and management of this condition remain challenging especially during infancy. Here, we report two unrelated patients, a 6-month-old Thai boy and a 5-year-old Emirati girl, with a history of failure to thrive, chronic fever, polydipsia, and polyuria presented in early infancy. The results of water deprivation test were compatible with a diagnosis of NDI. The entire coding regions of the AVPR2 and AQP2 gene were amplified by polymerase chain reaction and sequenced. Patient 1 was homozygous for a novel missense AQP2 mutation p.G96E, inherited from both parents. Patient 2 harbored a previously described homozygous p.T126M mutation in the AQP2 gene. Both patients were treated with a combination of thiazide diuretics and amiloride. Patient 1 developed paradoxical hyponatremia and severe dehydration 2 weeks after medical treatment began. In conclusion, we report a novel mutation of the AQP2 gene and highlight an important role of genetic testing for definite diagnosis. Vigilant monitoring of the fluid status and electrolytes after beginning the therapy is mandatory in infants with NDI.
We are grateful to Ms. Siraprapa Tongkobpetch and Mr. Chalurmpon Srichomthong for their technical assistance. This study was supported by the Thailand Research Fund (to V.S. and T.S.), National Research University Project of Thailand, Office of the Higher Education Commission (HR1163A), and Ratchadapisek Sompotch Fund (RES560530177HR), Faculty of Medicine, Chulalongkorn University.
Conflict of interest statement
Authors’ conflict of interest disclosure: None of the authors has personal or financial conflict of interests.
References
1. Wesche D, Deen PM, Knoers NV. Congenital nephrogenic diabetes insipidus: the current state of affairs. Pediatr Nephrol 2012;27:2183–204.10.1007/s00467-012-2118-8Search in Google Scholar PubMed
2. Babey M, Kopp P, Robertson GL. Familial forms of diabetes insipidus: clinical and molecular characteristics. Nat Rev Endocrinol 2011;7:701–14.10.1038/nrendo.2011.100Search in Google Scholar PubMed
3. Deen PM, Verdijk MA, Knoers NV, Wieringa B, Monnens LA, et al. Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science 1994;264:92–5.10.1126/science.8140421Search in Google Scholar PubMed
4. Robben JH, Knoers NV, Deen PM. Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 2006;291:F257–70.10.1152/ajprenal.00491.2005Search in Google Scholar PubMed
5. Onozaki A, Suzuki H, Imamura N, Katoh T, Watanabe T. Congenital nephrogenic diabetes insipidus with marked hyponatremia. Clin Exp Nephrol 2001;5:265–7.10.1007/s10157-001-8024-1Search in Google Scholar
6. Boussemart T, Nsota J, Martin-Coignard D, Champion G. Nephrogenic diabetes insipidus: treat with caution. Pediatr Nephrol 2009;24:1761–3.10.1007/s00467-009-1187-9Search in Google Scholar PubMed
7. Anton-Gamero M, Garcia-Martinez E, Fernandez-Ramos J, Rodríguez-Salas M, Gil-Campos M. Nephrogenic diabetes insipidus: the key element of paradoxical hyponatremia. Pediatr Nephrol 2009;24:2277–8.10.1007/s00467-009-1236-4Search in Google Scholar PubMed
8. Sahakitrungruang T, Wacharasindhu S, Sinthuwiwat T, Supornsilchai V, Suphapeetiporn K, et al. Identification of two novel aquaporin-2 mutations in a Thai girl with congenital nephrogenic diabetes insipidus. Endocrine 2008;33:210–4.10.1007/s12020-008-9074-xSearch in Google Scholar PubMed
9. Sahakitrungruang T, Tee MK, Rattanachartnarong N, Shotelersuk V, Suphapeetiporn K, et al. Functional characterization of vasopressin receptor 2 mutations causing partial and complete congenital nephrogenic diabetes insipidus in Thai families. Horm Res Paediatr 2010;73:349–54.10.1159/000308167Search in Google Scholar PubMed
10. Collins JS, Schwartz CE. Detecting polymorphisms and mutations in candidate genes. Am J Hum Genet 2002;71:1251–2.10.1086/344344Search in Google Scholar PubMed PubMed Central
11. Sasaki S. Aquaporin 2: from its discovery to molecular structure and medical implications. Mol Aspects Med 2012;33:535–46.10.1016/j.mam.2012.03.004Search in Google Scholar PubMed
12. Lin SH, Bichet DG, Sasaki S, Kuwahara M, Arthus MF, et al. Two novel aquaporin-2 mutations responsible for congenital nephrogenic diabetes insipidus in Chinese families. J Clin Endocrinol Metab 2002;87:2694–700.10.1210/jcem.87.6.8617Search in Google Scholar PubMed
13. Mulders SM, Knoers NV, Van Lieburg AF, Monnens LA, Leumann E, et al. New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels. J Am Soc Nephrol 1997;8:242–8.10.1681/ASN.V82242Search in Google Scholar PubMed
14. Sato N, Ishizaka H, Yagi H, Matsumoto M, Endo K. Posterior lobe of the pituitary in diabetes insipidus: dynamic MR imaging. Radiology 1993;186:357–60.10.1148/radiology.186.2.8421734Search in Google Scholar PubMed
15. Ranadive SA, Ersoy B, Favre H, Cheung CC, Rosenthal SM, et al. Identification, characterization and rescue of a novel vasopressin-2 receptor mutation causing nephrogenic diabetes insipidus. Clin Endocrinol (Oxf) 2009;71:388–93.10.1111/j.1365-2265.2008.03513.xSearch in Google Scholar PubMed PubMed Central
16. Kim GH, Lee JW, Oh YK, Chang HR, Joo KW, et al. Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co-transporter, and epithelial sodium channel. J Am Soc Nephrol 2004;15:2836–43.10.1097/01.ASN.0000143476.93376.04Search in Google Scholar PubMed
17. Morello JP, Salahpour A, Laperriere A, Bernier V, Arthus MF, et al. Pharmacological chaperones rescue cell surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest 2000;105:887–95.10.1172/JCI8688Search in Google Scholar PubMed PubMed Central
18. Yang B, Zhao D, Verkman AS. Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock-in mouse model of aquaporin-2 mutation. FASEB J 2009;23:503–12.10.1096/fj.08-118422Search in Google Scholar PubMed PubMed Central
©2014 by Walter de Gruyter Berlin Boston
