Clinical features and molecular basis of pseudohypoaldosteronism type 1

Abstract

Abstract.Pseudohypoaldosteronism (PHA) type 1 is a disease showing mineralocorticoid resistance in the kidney and/or other mineralocorticoid target tissues. Patients with PHA1 present very high plasma aldosterone and renin levels, but they develop excessive salt wasting. There are three types of PHA1. The systemic form of PHA1 is inherited in an autosomal recessive manner and causes severe life-long salt loss in multiple target tissues, such as sweat glands, salivary glands, the colonic epithelium, and the lung. In the systemic form of PHA1, life-long salt supplementation is necessary. The second type is the renal form, where aldosterone resistance is shown only in the kidney, and its inheritance is autosomal dominant. In the renal form of PHA1, salt supplementation generally becomes unnecessary by 1–3 yr of age. The third type is the secondary PHA1, which is strongly associated with urinary tract infections and/or urinary tract malformations. This review summarizes the clinical features and molecular basis of PHA1. Understanding of its pathogenesis can be helpful for the early diagnosis and clinical care of affected children with PHA1.

Gedeihstörung, Hyponatriämie, Hyperkaliämie – Differenzialdiagnostische Überlegungen einer seltenen genetischen Erkrankung

“…Neben Störungen bei der Aldosteronsynthese können eine Hypo natriämie und Hyperkaliämie bei suffizienter Hormonsynthese durch eine periphere Mineralokortikoidresistenz verursacht werden [1,8,9,12,13]. Die verschiedenen Formen dieses als Pseudohypoaldosteronismus bezeichneten Krankheitsbildes werden im Folgenden kurz erläutert:…”

Hyponatremia secondary to severe atopic dermatitis in early infancy

“…This pathophysiology is reminiscent of a rare variant of pseudohypoaldosteronism (PHA), which derives from mutations in CA12 encoding carbonic anhydrase 12 . Apart from classic PHA with aldosterone unresponsiveness in the distal nephron, which is caused by mutations either in the epithelial sodium channel genes ( ENaC‐α , ‐β , and ‐γ ) or in the aldosterone receptor gene ( NR3C2 ), the variant PHA is characterized by sodium loss exclusively from the sweat gland.…”

Complete clinical resolution of a Japanese family with renal pseudohypoaldosteronism type 1 due to a novel NR3C2 mutation

“…Autosomal dominant pseudohypoaldosteronism type 1 (adPHA1; OMIM #177735) is a rare condition characterized by congenital resistance to aldosterone resulting in excessive salt wasting . The renal form of adPHA1 (rPHA1) is considered as a mild phenotype of the disease due to renal‐limited mineralocorticoid resistance .…”

“…Autosomal dominant pseudohypoaldosteronism type 1 (adPHA1; OMIM #177735) is a rare condition characterized by congenital resistance to aldosterone resulting in excessive salt wasting . The renal form of adPHA1 (rPHA1) is considered as a mild phenotype of the disease due to renal‐limited mineralocorticoid resistance . Although patients with rPHA1 show severe salt wasting and failure to thrive, such representative clinical pictures subside with age despite persistent elevation of plasma aldosterone level (PAL) .…”

“…There were two mutations in this patient and two other members of his family. Because one of these mutations created a premature stop codon located on the N‐terminal domain, it is therefore plausible that this mutation inactivated mineralocorticoid receptor (MR) functionality . It has been reported that most adult patients with rPHA1, even if clinically silent, exhibit life‐long elevation of PAL .…”