SCNN1A Gene Mutation-Associated Neonatal Generalized Pseudoaldosteronism Type I: A Case Report and Literature Review
Pseudohypoaldosteronism (PHA) is an endocrine disorder characterized by genetic variations. The hallmark clinical manifestation is aldosterone resistance, leading to severe hyperkalemia, hyponatremia, and metabolic acidosis. Systemic pseudoaldosteronism type I (sPHA I) caused by mutations in the SCNN1A gene not only can leads to severe electrolyte disturbances, but also affects the respiratory, cardiac, digestive, and integumentary systems, resulting in an extremely high mortality rate. This report elucidates the diagnostic approach, acute-phase management, and crucial role of genetic counseling by presenting a typical case of a critically ill neonate.This report describes a 10-day-old male infant presenting with severe hyperkalemia, hyponatremia, and metabolic acidosis. His plasma renin and aldosterone levels were elevated, while 17-hydroxyprogesterone and cortisol levels were normal. Whole-exome sequencing analysis confirmed a diagnosis of pseudoaldosteronism. The infant had a compound heterozygous mutation in the SCNN1A gene: c.1360+1G>T in intron 8, a splicing mutation inherited from his mother(PVS1+PM2); c.509dup (p.Val171ArgfsTer35) in exon 3, a frameshift mutation inherited from his father(PVS1+PM2). According to the American College of Medical Genetics and Genomics (AGMG), both mutations were classified as pathogenic (PVS + 2PP) and were not reported in normal population databases. The infant was treated with potassium-lowering, acid correction, and sodium supplementation. His electrolyte levels normalized before discharge.sPHA I is rare, but it carries a high mortality rate. Early diagnosis and standardized treatment are critical for improving patient outcomes. We recommend that genetic testing should be initiated as early as possible; this is essential for establishing a diagnosis, guiding timely therapeutic interventions, and providing families with genetic counseling.