Increased Na reabsorption via the Na–Cl cotransporter in autosomal recessive pseudohypoaldosteronism

Abstract

Taken together, increased sodium reabsorption via the upregulation of the expression of NCC might have been responsible, at least in part, for the clinical improvement seen in an AR-PHA1 patient.

A homozygous missense mutation in SCNN1A is responsible for a transient neonatal form of pseudohypoaldosteronism type 1

“…The symptoms are usually persistent and more severe than in AD-PHA1. Recently, clinical improvement with age has been reported in patients with AR-PHA1 (2,18,28).…”

Clinical improvement in patients with autosomal recessive pseudohypoaldosteronism and the necessity for salt supplementation

“…Necessity for salt-supplementation: In Adachi's patient, salt supplementation was stopped at the age of 11 [1]. This patient's latest laboratory data (Na 131 mEq/l and K 5.5 mEq/l, with very high aldosterone levels) attest that he still needs salt supplementation.…”

“…To the Editor, In a recent article Adachi et al [1] reported clinical improvement with age in one patient with multi-system pseudohypoaldosteronism (PHA) carrying two heterozygous mutations in the c subunit of epithelial sodium channel (ENaC), noting that this patient ''may be the first example of clinical improvement in a molecularly proven AR-PHA1.'' We would like to draw attention to four major issues of age-dependent amelioration in multi-system PHA raised by this study.…”

“…Physiological mechanism of the age-dependent amelioration: The study of Adachi et al [1] provides the first evidence for a compensatory increased expression of the Na ? -Cl -cotransporter.…”

“…Activity of truncated ENaC subunit: Adachi et al [1] note that a mutation that leads to the truncation of an ENaC subunit (without the second trans-membrane domain) should ''lead to the complete loss of its function''. Recently we showed that a truncated human b-ENaC subunit may support low partial activity of ENaC expressed in Xenopus oocytes [3].…”