ESPE Abstracts

Background: Hereditary Nephrogenic Diabetes Insipidus (HNDI) is an uncommon disorder due to a resistance to anti diuretic hormone (ADH) leading to a reduced urinary concentrating ability. The X-linked form is fully expressed in hemizygous male patients, but diabetes insipidus may also present in heterozygous females where it must be distinguished from autosomal and other secondary causes.

Objective and hypotheses: We report a mother and daughter with HNDI due to a heterozygous deletion in exon 1 of the arginine vasopressin receptor 2 (AVPR2) gene not previously described.

Method: A 5-year-old girl was referred for investigation of polyuria and polydipsia from her infancy. Her mother showed similar symptoms that had not been previously investigated. The patient had a water deprivation test elsewhere at age 3 that was inconclusive. Thyroid, cortisol, renal, and calcium profiles were normal. Hypertonic saline test was performed, the results of which are shown below.

Results: AQP2 (Aquaporin) and initial AVPR2 gene sequencing had not identified a mutation, but subsequent quantitative PCR analysis revealed a heterozygous large exon 1 deletion of the AVPR2 gene. The same deletion was also found in the mother. Results of skewed X inactivation studies on mother and daughter are awaited. The patient’s symptoms have significantly improved on appropriate treatment.

Conclusion: It is important to note that the clinical phenotype of HNDI in a symptomatic female may be due to non-random X chromosome inactivation, thereby allowing expression of the mutant X chromosome. Deletions in AVPR2 gene with skewed X inactivation, although rare, should be considered in symptomatic females with HNDI.