Disorders of the Epithelial Na+ Channel in Liddle’s Syndrome and Autosomal Recessive Pseudohypoaldosteronism Type 1

2000 ◽  
Vol 8 (6) ◽  
pp. 320-325 ◽  
Author(s):  
Young S. Oh ◽  
David G. Warnock
Keyword(s):  
Autosomal Recessive ◽  
Liddle’S Syndrome ◽  
Liddle's Syndrome ◽  
Pseudohypoaldosteronism Type

scholarly journals Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1

2013 ◽  
Vol 168 (5) ◽  
pp. 707-715 ◽  
Author(s):  
Maik Welzel ◽  
Leyla Akin ◽  
Anja Büscher ◽  
Tülay Güran ◽  
Berthold P Hauffa ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Current Knowledge ◽  
Monogenic Disease ◽  
Α Subunit ◽  
Recessive Mutations ◽  
Neonatal Onset ◽  
Genes Encoding ◽  
Heterozygous Carriers ◽  
Pseudohypoaldosteronism Type

BackgroundPseudohypoaldosteronism type 1 (PHA1) is a monogenic disease caused by mutations in the genes encoding the human mineralocorticoid receptor (MR) or the α (SCNN1A), β (SCNN1B) or γ (SCNN1G) subunit of the epithelial Na+ channel (ENaC). While autosomal dominant mutation of the MR cause renal PHA1, autosomal recessive mutations of the ENaC lead to systemic PHA1. In the latter, affected children suffer from neonatal onset of multi-organ salt loss and often exhibit cystic fibrosis-like pulmonary symptoms.ObjectiveWe searched for underlying mutations in seven unrelated children with systemic PHA1, all offsprings of healthy consanguineous parents.Methods and resultsAmplification of the SCNN1A gene and sequencing of all 13 coding exons unraveled mutations in all of our patients. We found five novel homozygous mutations (c.587_588insC in two patients, c.1342_1343insTACA, c.742delG, c.189C>A, c.1361-2A>G) and one known mutation (c.1474C>T) leading to truncation of the αENaC protein. All parents were asymptomatic heterozygous carriers of the respective mutations, confirming the autosomal recessive mode of inheritance. Five out of seven patients exhibited pulmonary symptoms in the neonatal period.ConclusionThe α subunit is essential for ENaC function and mutations truncating the pore-forming part of the protein leading to systemic PHA1. Based on current knowledge, the pulmonary phenotype cannot be satisfactorily predicted.

Severe Autosomal Recessive Pseudohypoaldosteronism Type 1 Caused by Mutations in the Mineralocorticoid Receptor Gene

2011 ◽  
pp. P3-13-P3-13
Author(s):  
Edwige-Ludiwyne Hubert ◽  
Raphael Teissier ◽  
Fabio Luis Fernandes-Rosa ◽  
Michel Fay ◽  
Marie-Edith Rafestin-Oblin ◽  
...  
Keyword(s):  
Mineralocorticoid Receptor ◽  
Autosomal Recessive ◽  
Receptor Gene ◽  
Pseudohypoaldosteronism Type

scholarly journals Reducing αENaC expression in the kidney connecting tubule induces pseudohypoaldosteronism type 1 symptoms during K+ loading

2016 ◽  
Vol 310 (4) ◽  
pp. F300-F310 ◽  
Author(s):  
Søren Brandt Poulsen ◽  
Jeppe Praetorius ◽  
Helle H. Damkier ◽  
Lance Miller ◽  
Raoul D. Nelson ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Collecting Duct ◽  
Fractional Excretion ◽  
Standard Diet ◽  
Α Subunit ◽  
Connecting Tubule ◽  
Relative Body Weight ◽  
Output Only ◽  
Pseudohypoaldosteronism Type

Genetic inactivation of the epithelial Na+ channel α-subunit (αENaC) in the renal collecting duct (CD) does not interfere with Na+ and K+ homeostasis in mice. However, inactivation in the CD and a part of the connecting tubule (CNT) induces autosomal recessive pseudohypoaldosteronism type 1 (PHA-1) symptoms in subjects already on a standard diet. In the present study, we further examined the importance of αENaC in the CNT. Knockout mice with αENaC deleted primarily in a part of the CNT (CNT-KO) were generated using Scnn1alox/lox mice and Atp6v1b1:: Cre mice. With a standard diet, plasma Na+ concentration ([Na+]) and [K+], and urine Na+ and K+ output were unaffected. Seven days of Na+ restriction (0.01% Na+) led to a higher urine Na+ output only on days 3–5, and after 7 days plasma [Na+] and [K+] were unaffected. In contrast, the CNT-KO mice were highly susceptible to a 2-day 5% K+ diet and showed lower food intake and relative body weight, lower plasma [Na+], higher fractional excretion (FE) of Na+, higher plasma [K+], and lower FE of K+. The higher FE of Na+ coincided with lower abundance and phosphorylation of the Na+-Cl− cotransporter. In conclusion, reducing ENaC expression in the CNT induces clear PHA-1 symptoms during high dietary K+ loading.

scholarly journals A novel SCNN1A variation in a patient with autosomal-recessive pseudohypoaldosteronism type 1

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Mohammed Ayed Huneif ◽  
Ziyad Hamad AlHazmy ◽  
Anas M. Shoomi ◽  
Mohammed A. AlGhofely ◽  
Humariya Heena ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Pseudohypoaldosteronism Type

Liddle's syndrome: late diagnosis of a rare cause of arterial hypertension

2002 ◽  
Vol 78 (3) ◽  
pp. 251-4 ◽  
Author(s):  
Ana C. S. Silva ◽  
Eduardo A. Oliveira ◽  
Camila R. Gomes ◽  
Flávio Souza Lima ◽  
José S.S. Diniz
Keyword(s):  
Arterial Hypertension ◽  
Late Diagnosis ◽  
Liddle’S Syndrome ◽  
Liddle's Syndrome
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