SCNN1G – Pseudohypoaldosteronism Type IB1

SCNN1G is implicated in autosomal recessive pseudohypoaldosteronism type IB1, a systemic salt‐wasting disorder marked by hypovolemia and hyperkalemia. Two unrelated infants harboring homozygous SCNN1G loss‐of‐function variants presented with severe volume depletion refractory to mineralocorticoid therapy ([PMID:31900739]; [PMID:31522814]). Functional assays in vitro and in vivo confirmed that these γ‐ENaC defects reduce channel activity, trigger renal tubular cell apoptosis, and underlie the observed nephropathy. Mechanistic studies further indicate that dietary potassium restriction ameliorates sodium wasting by upregulating compensatory NCC and pendrin transport in the distal nephron ([PMID:31900739]). These data support limited genetic evidence but consistent functional concordance, justifying clinical genetic testing for early diagnosis and dietary management. Key Take-home: SCNN1G sequencing informs diagnosis and guides tailored therapy in pediatric PHA1.

References

• CEN case reports • 2020 • Dietary potassium restriction attenuates urinary sodium wasting in the generalized form of pseudohypoaldosteronism type 1 PMID:31900739
• Biochemical and biophysical research communications • 2019 • A novel SCNN1G mutation in a PHA I infant patient correlates with nephropathy PMID:31522814

Evidence Based Scoring (AI generated)