Diagnostic Pitfalls of a Newborn with Congenital Nephrogenic Diabetes Insipidus

Abstract

Congenital nephrogenic diabetes insipidus (NDI) is a rare cause of hypernatremia in newborns. Central diabetes insipidus (CDI) is the main differential diagnosis in NDI, however NDI responds poorly to desmopressin acetate (DDAVP) treatment, while this is the mainstay of CDI management. Therefore, early and correct diagnosis of NDI is important to avoid the complications of inappropriate therapy. We report a newborn with hypernatremia and hypotonic polyuria. The patient was initially responsive but subsequently unresponsive to intranasal DDAVP treatment in terms of both urine output and serum sodium levels. A novel hemizygous missense mutation (c.632T>C, p.L211P) in the AVPR2 gene was found in both the baby and his mother, and the diagnosis of congenital NDI was established. After hydrochlorothiazide treatment and hypo-osmolar formula were given, urine volume was decreased, and serum sodium levels were normalized. Early recognition and appropriate management of NDI may prevent complications of hypernatremic dehydration in young infants.

Keywords: AVPR2; Nephrogenic diabetes insipidus; hypernatremia; neonate.

Figure 1

Clinical characteristics of the patient with nephrogenic diabetes insipitus due to mutation in AVPR2 gene. A) Pedigree of the patient and his family. Individual IV.2 is heterozygous for AVPR2 c.632T>C. Individual V.2 is hemizygous for AVPR2 c.632T>C. Genetic analysis could not be performed in II.6, III.4, III.5, and IV.3. Slash-line square (IV.3) indicates maternal uncle with polyuria, polydipsia and mental retardation. B) The urine output and serum sodium concentrations of the patient with nephrogenic diabetes insipidus during the clinical follow-up

Figure 2

Molecular characteristics of wild type and mutant AVPR2 gene and AVPR2 protein. A) Diagram of hAVPR2 gene (NM_000054.6): Arrow shows novel missense variant (L211P) identified in the patient and his mother. B) Structure of AVPR2: Dark grey and light grey indicates extracellular and cytoplasmic components of AVPR2, respectively. H: Transmembrane helical components of AVPR2; painted with corresponding colors of the helixes in three-dimensional structure of protein. Partial alignment of AVPR2 protein sequences, generated by Clustal Omega (https://www.ebi.ac.uk/Tools/msa/clustalo/), showing conservation of leucine (Leu; L) at position 211, highlighted in grey. C) Three-dimensional protein structures for wild-type and mutant proteins were obtained with Swiss-Model and UCSF Chimera 1.10.2 servers, and rainbow-painted from dark blue for N-terminal to red for C-terminal. The Leu211 and Pro211 residues are presented in a magnified frame for viewing at a higher quality and indicated in yellow