pseudohypoaldosteronism 1—autosomal recessive
ENDOCRINOLOGY, METABOLISM, PHYSIOLOGY
A rare severe salt wasting condition (OMIM:264350) caused by end organ unresponsiveness to mineralocorticoids, resulting in multi-system disease, and an often fulminant presentation in the neonatal period with dehydration, hyponatraemia, hyperkalaemia, metabolic acidosis, failure to thrive and weight loss.
The channelopathy primarily affects the renin-aldosterone system and urinary Na+/K+ ratios, resulting in distinct genotype-phenotype relationships in PHA1 patients. Loss-of-function mutations are associated with a severe clinical course and age-dependent hyperactivation of the renin-aldosterone system. This feature is not observed in patients with missense mutations that merely reduce channel activity. Markedly reduced channel activity results in impaired linear growth and delayed puberty.
Molecular pathology Defects of SCNN1A, SCNN1B, and SCNN1G, which respectively encode the alpha, beta and gamma subunits of a nonvoltage-gated, amiloride-sensitive sodium channel that controls fluid and electrolyte transport across epithelia in the kidney, lung, and other tissues, cause pseudohypoaldosteronism 1—autosomal recessive.