Pseudohypoaldosteronism: family studies to identify asymptomatic carriers by stimulation of the renin-aldosterone system.
Defective aldosterone receptor binding is present in pseudohypoaldosteronism, and sporadic as well as familial cases have been reported. In familial pseudohypoaldosteronism, autosomal dominant as well as autosomal recessive inheritance has been described. The autosomal dominant form is characterized by a relative mild course of the disease and asymptomatic carriers of the defect in these families, whereas the autosomal recessive form is characterized by severe salt-losing symptoms; not uncommonly these families are consanguineous. To date no genetic mutation has been identified in the aldosterone receptor gene of affected patients. Studies to evaluate the biochemical defect and to characterize the inheritance pattern are of major interest for clinical as well as research purposes. Thus we studied the response of the renin-angiotensin-aldosterone system to sodium depletion using a single dose of furosemide. In 5 patients from five nonconsanguineous families and in all available family members the renin and aldosterone levels as well as serum sodium was measured before and after an oral dose of furosemide. The aldosterone receptor binding of peripheral mononuclear leukocytes was determined at the beginning of the study. In three families asymptomatic carriers of the defect could be identified in the baseline state by elevated levels of basal aldosterone and high renin concentration. The levels of renin and aldosterone did not differ between the symptomatic and asymptomatic individuals in these families. Interestingly the aldosterone receptor binding in the asymptomatic carriers of these families was normal. In the other two families, however, the basal hormonal data were normal in all relatives suggesting at first sporadic cases. During sodium depletion with furosemide, renin as well as aldosterone levels rose significantly in 1 parent and a sibling, respectively. In contrast to the first three families the aldosterone receptor binding in these family members was low. We propose to reclassify these family members as asymptomatic carriers and the patients as familial cases. Whether these cases are genetically identical to the 'classical autosomal dominant cases' remains to be seen. It seems that the pathogenesis of pseudohypoaldosteronism is even more heterogeneous than previously thought and factors other than aldosterone receptor binding are crucial and need further identification.
University Children's Hospital, Munich, Germany.
U
U
Kuhnle
G K
GK
Hinkel
W
W
Hubl
T
T
Reichelt
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005665:Furosemide; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011546:Pseudohypoaldosteronism / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology*
D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D005665:Furosemide; D012083:Renin