Prenatal Diagnosis of Autosomal Dominant Pseudohypoaldosteronism due to NR3C2 Gene Mutation: Immediate Postnatal Oral Saline Therapy Prevents the Clinical Manifestations Resulting from Impaired Salt Balance.

Abstract

Introduction: PHAI encompasses two distinct forms of aldosterone resistance, with unique clinical and endocrine manifestations and genetic patterns, autosomal dominant (AD) and autosomal recessive. The AD form is caused by heterozygous mutations on the NR3C2 gene on chromosome 4q31, coding for the aldosterone receptor. The salt-wasting symptoms usually present in early infancy. The patients require intravenous/oral sodium chloride therapy until the age of 1-3 years. In the absence of family history, the diagnosis is delayed in many infants for even months. The importance of prenatal diagnosis in pregnancies with other affected family members has not been evaluated. We hereby report the effect of prenatal molecular diagnosis and immediate oral salt therapy on the postnatal disease course.

Case report: The patient was born at 39 weeks. Pregnancy and delivery were uneventful. The birth weight was 3,038 g. Family history was significant for a large heterozygous deletion encompassing exons 4 to 9 of the NR3C2 gene in her mother and brother. They were symptomatic at birth. We evaluated the MR gene analysis in the fetus by amniocentesis, which showed the same mutation found in the mother. Oral salt therapy was started on day 1. The growth parameters and sodium concentrations remained normal for 8 months with normal to borderline high potassium.

Conclusion: Prenatal genetic diagnosis and prompt salt supplementation after birth prevent the clinical manifestations resulting from salt wasting.