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.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Aldosterone / metabolism
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Aldosterone / pharmacology*
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Aldosterone / physiology
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Animals
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Drug Resistance / genetics*
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Drug Resistance / physiology
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Epithelial Sodium Channels / genetics
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Genetic Association Studies
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Humans
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Models, Biological
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Mutant Proteins / chemistry
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Mutant Proteins / genetics
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Mutant Proteins / metabolism
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Mutant Proteins / physiology
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Mutation / physiology
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Protein Interaction Domains and Motifs / genetics
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Protein Interaction Domains and Motifs / physiology
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Pseudohypoaldosteronism / genetics
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Pseudohypoaldosteronism / physiopathology
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Receptors, Mineralocorticoid / genetics*
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Receptors, Mineralocorticoid / metabolism
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Receptors, Mineralocorticoid / physiology*
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Structure-Activity Relationship
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Water-Electrolyte Balance / genetics
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Water-Electrolyte Balance / physiology
Substances
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Epithelial Sodium Channels
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Mutant Proteins
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Receptors, Mineralocorticoid
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Aldosterone