Family form of nephrogenic Х-linked diabetes insipidus

There is a global trend towards an increase in the prevalence of diabetes insipidus. Symptoms of nephrogenic diabetes insipidus with X-linked inheritance appear in men, in women with heterozygous mutations, are characterized by an isolated symptom complex of polyuria, polydipsia, hypostenuria. In children, more often than in adults, with fluid restriction, a clinic of water-deficient dehydration develops with hypernatremia, hyperthermia, and plasma hyperosmolality. This manuscript presents a case of Nephrogenic diabetes insipidus, X-linked familial form in male patients.At the same time, in the family along the female line, the mother and grandmother also had an increased need for water, the use of minirin was ineffective. In the older brother and younger brother, clinical manifestations of diabetes insipidus in the form of severe thirst and polyuria were noted from infancy, after the examination, the diagnosis was made — diabetes insipidus and desmopressin was prescribed.Due to the lack of effect from the use of desmopressin, the analysis of exons and adjacent sections of the introns of the AQP2 and AVPR2 genes was carried out by PCR and subsequent direct sequencing. No mutations were found in the AQP2 gene. The hemizygous substitution S315I was found in the AVPR2 gene. The familial form X was confirmed — linked nephrogenic diabetes insipidus. A hypothiazide was recommended, against the background of constant intake of which only a slight positive trend is observed.

1. Dedov II, Mel’nichenko GA, Pigarova EA, et al. Federal clinical guidelines on diagnosis and treatment of diabetes insipidus in adults. Obesity and metabolism. 2018;15(2):56-71. (In Russ.). doi: https://doi.org/10.14341/omet9670

2. Kiriliuk ML. Tsentral’nyi nesakharnyi diabet. Mezhdunarodnyi endokrinologicheskii zhurnal. 2013;5(53):64-69. (In Russ.).

3. Bockenhauer D, Bichet DG. Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. Nat Rev Nephrol. 2015;11(10):576-588. doi: https://doi.org/10.1038/nrneph.2015.89

4. Knoers N, Levtchenko EN. Nephrogenic diabetes insipidus. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N. Pediatric nephrology: 6-th edition. Berlin-Heidelberg: Springer-Verlag; 2009. P. 1005-1018.

5. Wesche D, Deen P, Knoers N. Сongenital nephrogenic diabetes insipidus: the current state of affairs. Pediatr Nephrol. 2012;27(12):2183-2204. doi: https://doi.org/10.1007/s00467-012-2118-8

6. Bichet DG, Bockenhauer D. Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant). Best Pract Res Clin Endocrinol Metab. 2016;30(2):263-276. doi: https://doi.org/10.1016/j.beem.2016.02.010

7. Janchevska A, Tasic V, Gucev Z, et al. X-Linked Recessive Form of Nephrogenic Diabetes Insipidus in A 7-Year-Old Boy. Balk J Med Genet. 2014;17(2):81-85. doi: https://doi.org/10.2478/bjmg-2014-0078

8. Tyulpakov AN, Rubtsov PM, Shandin AN. Familial type of nephrogenic diabetes insipidus with partially preserved renal concentration function, which is caused by homozygous D150E mutation in the aquaporin-2 (AQP-2) gene. Problems of Endocrinology. 2007;53(5):13-18. (In Russ.). doi: https://doi.org/10.14341/probl200753513-18

9. Savenkova ND, Semenova OA, Stepanova AA. Congenital nephrogenic diabetes insipidus in children and adolescents. The new strategy of therapy. Nephrology (Saint-Petersburg). 2017;21(3):9-17. (In Russ.). doi: https://doi.org/10.24884/1561-6274-2017-3-9-17