Case Report: Compound Heterozygous SCNN1B Mutations Causing Pseudohypoaldosteronism Type 1B2 in Neonatal Twins.

BACKGROUND: Pseudohypoaldosteronism type I (PHA1) is a rare genetic disorder characterized by renal or systemic resistance to aldosterone, resulting in hyponatremia, hyperkalemia, and metabolic acidosis. The autosomal recessive systemic form (PHA1B), caused by mutations in SCNN1A, SCNN1B, or SCNN1G, is particularly severe and typically manifests in the neonatal period. Among these, SCNN1B-related cases occur less frequently than SCNN1A-related cases.

CASE PRESENTATION: We report a pair of dizygotic preterm twins (male and female) born at 35 + 5 weeks of gestation who presented at 8 days of age with poor feeding, weight loss, and severe jaundice. Both developed life-threatening hyperkalemia, hyponatremia, and metabolic acidosis, and these conditions were unresponsive to initial management including hydrocortisone. Laboratory findings showed markedly elevated plasma renin and aldosterone levels, with no evidence of congenital adrenal hyperplasia or other metabolic disorders. Whole-exome sequencing revealed compound heterozygous mutations in the SCNN1B gene: a splice-site variant (c.585+2T>C) inherited from the mother and a missense variant (c.1544T>C, p.Ile515Thr) from the father. Both mutations are novel and were confirmed by Sanger sequencing. Diagnosis of systemic PHA1B2 was established. Treatment with oral sodium chloride, sodium citrate, and potassium-binding resins led to gradual correction of electrolyte imbalance and clinical stabilization.

CONCLUSION: These are the first reported Chinese cases of neonatal-onset PHA1B due to novel compound heterozygous SCNN1B mutations. This report broadens the mutational spectrum of SCNN1B and underscores the importance of early genetic testing in refractory neonatal electrolyte disturbances.