Nephrogenic Syndrome of Inappropriate Antidiuresis in a Female Neonate: Review of the Clinical Presentation in Females

Abstract

Background: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare X-linked disease due to gain-of-function mutations in the AVP V2 receptor gene. Hemizygous males present with recurrent episodes of severe hyponatremia in infancy. Heterozygous females are usually asymptomatic. Case Report: We report on a 23-day-old female neonate, born at term with 3,260 g that presented with recurrent hyponatremia (Na between 124 and 134 mmol/l) due to NSIAD. She was a heterozygous carrier of the c.409 C>T mutation in the AVPR2 gene. Conclusions: This is the first report of a female neonate presenting with hyponatremia due to NSIAD. The diagnosis of NSIAD should not be limited to male infants and should also be considered in female infants with the clinical picture of inappropriate antidiuresis.

Nephrogenic syndrome of inappropriate antidiuresis secondary to an activating mutation in the arginine vasopressin receptor AVPR2

“…30 Importantly, female subjects harbouring heterozygous activating AVPR2 mutations have also been reported to exhibit reduced water excretion in response to an oral load, and may thus be similarly affected to some male hemizygotes. 25,30,32 Fluid restriction is the mainstay of treatment for NSIAD and can be effective in attenuating the risk of hyponatraemia, as in our patient. Oral urea, which reduces natriuresis while maintaining aquaresis, is an alternative, especially in paediatric cases where strict fluid restriction may be hazardous or difficult to achieve.…”

“…To date, fewer than 30 cases of NSIAD due to activating AVPR2 mutations have been reported ,. While the majority of affected individuals harbour mutations at codon 137, activating mutations affecting other amino acids (p.Phe299Val and p.Ile130Asn) have also been described .…”

“…Accordingly, it seems that a subgroup of those with activating AVPR2 mutations only come to attention in adult life after an unusually severe water load or in the context of exogenous salt loss, suggesting there may be a protective element of chronic voluntary fluid restriction in these subjects . Importantly, female subjects harbouring heterozygous activating AVPR2 mutations have also been reported to exhibit reduced water excretion in response to an oral load, and may thus be similarly affected to some male hemizygotes …”

“…To date, fewer than 30 cases of NSIAD due to activating AVPR2 mutations have been reported. 10,[23][24][25][26][27][28][29][30][31][32] While the majority of affected individuals harbour mutations at codon 137, activating mutations affecting other amino acids (p.Phe299Val and p.Ile130Asn) have also been described. 22,33 It is interesting to note the marked heterogeneity with respect to age at diagnosis and severity of the disorder between subjects.…”

Nephrogenic syndrome of inappropriate antidiuresis secondary to an activating mutation in the arginine vasopressin receptor AVPR2

“…To date, fewer than 30 cases of NSIAD due to activating AVPR2 mutations have been reported 10,[23][24][25][26][27][28][29][30][31][32] . Whilst the majority of affected individuals harbour mutations at codon 137, activating mutations affecting other amino acids (p.Phe299Val and p.Ile130Asn) have also been described 22,33 .…”