Clinical, Biochemical, and Molecular Spectrum of Pseudohypoaldosteronism Type 1B in Indian Children: A Multicentric Case Series.

BACKGROUND

Pseudohypoaldosteronism type 1 (PHA1) is a rare hereditary disorder characterised by aldosterone resistance leading to salt wasting, hyperkalaemia, and metabolic acidosis. Two forms are recognised: a milder renal form (PHA1A) due to NR3C2 mutations and a severe systemic form (PHA1B) caused by biallelic mutations in epithelial sodium channel (ENaC) subunit genes. Data on Indian patients are scarce. This study describes the clinical, biochemical, and molecular characteristics and treatment outcomes of children with PHA1 from South India.

METHODS

This multicentric retrospective series included nine children diagnosed with PHA1 across six tertiary care centres between 2022 and 2025. Clinical and biochemical data were extracted from hospital records. Plasma renin, aldosterone, cortisol, and 17-hydroxyprogesterone were measured at presentation. Genetic testing was performed using clinical exome sequencing, and variants were classified according to American College of Medical Genetics and Genomics (ACMG) guidelines.

RESULTS

All nine patients had the systemic form (PHA1B). The median age at presentation was 14 days (interquartile range 5.5-42.5), and parental consanguinity was present in seven (78%). All presented with hyponatraemia and hyperkalaemia (median serum sodium 124 mEq/L; potassium 8.0 mEq/L). Eight (pathogenic/likely-pathogenic: 4, supporting: 4) homozygous variants were identified in SCNN1A (n = 2), SCNN1B (n = 3), and SCNN1G (n = 3); all were novel. Six patients (67%) died, mainly due to sepsis (n = 2) or treatment discontinuation (n = 4), while three remain stable on oral sodium supplementation.

CONCLUSIONS

This first multicentric South Indian series highlights exclusive reporting of PHA1B, high early mortality, and major treatment challenges. Eight novel ENaC variants expand the genetic spectrum of PHA1B in India.