title: Aldosterone resistance: structural and functional considerations and new perspectives.
abstract: Aldosterone plays an essential role in the maintenance of fluid and electrolyte homeostasis in the distal nephron. Loss-of-function mutations in two key components of the aldosterone response, the mineralocorticoid receptor and the epithelial sodium channel ENaC, lead to type 1 pseudohypoaldosteronism (PHA1), a rare genetic disease of aldosterone resistance characterized by salt wasting, dehydration, failure to thrive, hyperkalemia and metabolic acidosis. This review describes the clinical, biological and genetic characteristics of the different forms of PHA1 and highlights recent advances in the understanding of the pathogenesis of the disease. We will also discuss genotype-phenotype correlations and new clinical and genetic entities that may prove relevant for patient's care in neonates with renal salt losing syndromes and/or failure to thrive.
authors.affiliation: INSERM U970, Paris Cardiovascular Research Center, Paris, France. maria-christina.zennaro@inserm.fr
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Zennaro
authors.forename: Edwige-Ludiwyne
authors.initials: EL
authors.lastname: Hubert
authors.forename: Fábio L
authors.initials: FL
authors.lastname: Fernandes-Rosa
mesh_terms: D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D004351:Drug Resistance / Q000235:genetics* / Q000502:physiology; D053503:Epithelial Sodium Channels / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D008954:Models, Biological; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009154:Mutation / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000235:genetics / Q000502:physiology; D011546:Pseudohypoaldosteronism / Q000235:genetics / Q000503:physiopathology; D018161:Receptors, Mineralocorticoid / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D013329:Structure-Activity Relationship; D014882:Water-Electrolyte Balance / Q000235:genetics / Q000502:physiology
chemical_list: D053503:Epithelial Sodium Channels; D050505:Mutant Proteins; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone