Autosomal dominant pseudohypoaldosteronism type 1 in an infant with salt wasting crisis associated with urinary tract infection and obstructive uropathy.
Type 1 pseudohypoaldosteronism (PHA1) is a salt wasting syndrome caused by renal resistance to aldosterone. Primary renal PHA1 or autosomal dominant PHA1 is caused by mutations in mineralocorticoids receptor gene (NR3C2), while secondary PHA1 is frequently associated with urinary tract infection (UTI) and/or urinary tract malformations (UTM). We report a 14-day-old male infant presenting with severe hyperkalemia, hyponatremic dehydration, metabolic acidosis, and markedly elevated serum aldosterone level, initially thought to have secondary PHA1 due to the associated UTI and posterior urethral valves. His serum aldosterone remained elevated at 5 months of age, despite resolution of salt wasting symptoms. Chromosomal microarray analysis revealed a deletion of exons 3-5 in NR3C2 in the patient and his asymptomatic mother who also had elevated serum aldosterone level, confirming that he had primary or autosomal dominant PHA1. Our case raises the possibility that some patients with secondary PHA1 attributed to UTI and/or UTM may instead have primary autosomal dominant PHA1, for which genetic testing should be considered to identify the cause, determine future recurrence risk, and possibly prevent the life-threatening salt wasting in a subsequent family member. Future clinical research is needed to investigate the potential overlapping between secondary PHA1 and primary autosomal dominant PHA1.
Division of Endocrinology, Nationwide Children's Hospital/The Ohio State University College of Medicine, Columbus, OH 43205, USA.
Sasigarn A
SA
Bowden
Division of Neonatology, Nationwide Children's Hospital/The Ohio State University College of Medicine, Columbus, OH 43205, USA.
Corin
C
Cozzi
Division of Molecular & Human Genetics, Department of Pediatrics, Nationwide Children's Hospital/The Ohio State University College of Medicine, Columbus, OH 43205, USA.
Scott E
SE
Hickey
Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital/The Ohio State University College of Medicine, Columbus, OH 43205, USA.
Devon Lamb
DL
Thrush
Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital/The Ohio State University College of Medicine, Columbus, OH 43205, USA.
Caroline
C
Astbury
Division of Neonatology, Nationwide Children's Hospital/The Ohio State University College of Medicine, Columbus, OH 43205, USA.
Sushma
S
Nuthakki