Systemic Pseudohypoaldosteronism Type I: A Case Report and Review of the Literature

Nur, Nasifa; Lang, Cameron; Hodax, Juanita K.; Quintos, Jose Bernardo

doi:10.1155/2017/7939854

Cited by 19 publications

(23 citation statements)

References 35 publications

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“…This phenomenon has been recapitulated in a murine model overexpressing the β-subunit of the ENaC protein [23,26]. Conversely, mutations causing hypoactivity of the ENaC channel have been shown to cause pseudohypoaldosteronism [6,24,29], which expands the ASL depth and accelerates the MC [29]. Further, recent evidence has emerged demonstrating that CF patients who possess rare mutations in the SCNN1D gene, which encodes the δ subunit of ENaC, have hypomorphic ENaC channel activity [17].…”

Section: Introductionmentioning

confidence: 99%

The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis

Shei

Peabody

Kaza

et al. 2018

Current Opinion in Pharmacology

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Cystic fibrosis (CF) is a monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR dysfunction is characterized by abnormal mucociliary transport due to a dehydrated airway surface liquid (ASL) and hyperviscous mucus, among other pathologies of host defense. ASL depletion is caused by the absence of CFTR medicated chloride secretion along with continued activity of the epithelial sodium channel (ENaC) activity, which can also be affected by CFTR mediated anion conductance. Therefore, ENaC has been proposed as a therapeutic target to ameliorate ASL dehydration and improve mucus transport. Inhibition of ENaC has been shown to restore ASL hydration and enhance mucociliary transport in induced models of CF lung disease. To date, no therapy inhibiting ENaC has successfully translated to clinical efficacy, in part due to concerns regarding off-target effects, systemic exposure, durability of effect, and adverse effects. Recent efforts have been made to develop novel, rationally designed therapeutics to produce specific, long-lasting inhibition of ENaC activity in the airways while simultaneously minimizing off target fluid transport effects, systemic exposure and side effects. Such approaches comprise next-generation small molecule direct inhibitors, indirect channel-activating protease inhibitors, synthetic peptide analogs, and oligonucleotide-based therapies. These novel therapeutics represent an exciting step forward in the development of ENaC-directed therapies for CF.

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Section: Introductionmentioning

confidence: 99%

The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis

Shei

Peabody

Kaza

et al. 2018

Current Opinion in Pharmacology

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“…To date, more than 40 variants have been reported in the genes encoding ENaC subunits ( 9 ), and these variants have most often been found in the gene encoding the alpha subunit. Eleven variants have been reported in the gene encoding the beta subunit ( Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical Management in Systemic Type Pseudohypoaldosteronism Due to <i>SCNN1B</i> Variant and Literature Review

Küçükali¹,

Çeti̇nkaya²,

Tunç³

et al. 2021

Jcrpe

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Systemic pseudohypoaldosteronism (PHA) is a rare, salt-wasting syndrome that is caused by inactivating variants in genes encoding epithelial sodium channel subunits. Hyponatremia, hyperkalemia, metabolic acidosis, increased aldosterone and renin levels are expected findings in PHA. Clinical management is challenging due to high dose oral replacement therapy. Furthermore, patients with systemic PHA require life-long therapy. Here we report a patient with systemic PHA due to SCNN1B variant whose hyponatremia and hyperkalemia was detected at the 24 th hour of life. Hyperkalemia did not improve with conventional treatments and dialysis was required. He also developed myocarditis and hypertension in follow-up. Challenges for diagnosis and treatment in this patient are discussed herein. In addition, published evidence concerning common features of patients with SCNN1B variant are reviewed.

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“…Generally, salt replacement therapy ceases between 1 to 3 yr of age, demonstrating a good prognosis in renal PHA1 ( 2 , 4 ). However, PHA1, which results from mutations in the three genes encoding the subunits of the epithelial sodium channel ENaC ( SCNN1A , SCNN1B, and SCNN1G ), is a clinically severe form with no remission ( 5 , 12 , 13 ). Patients with systemic PHA1 need a larger amount of salt replacement than that required in patients with renal PHA1 ( 12 , 13 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, PHA1, which results from mutations in the three genes encoding the subunits of the epithelial sodium channel ENaC ( SCNN1A , SCNN1B, and SCNN1G ), is a clinically severe form with no remission ( 5 , 12 , 13 ). Patients with systemic PHA1 need a larger amount of salt replacement than that required in patients with renal PHA1 ( 12 , 13 ). Our experience shows that genetic analysis is useful to reach a differential diagnosis between renal PHA1 and systemic PHA1.…”

Section: Discussionmentioning

confidence: 99%

An infantile case of pseudohypoaldosteronism type 1 (PHA1) caused by a novel mutation of <i>NR3C2</i>

Goda

Komatsu

Nozu

et al. 2020

Clin Pediatr Endocrinol

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Systemic Pseudohypoaldosteronism Type I: A Case Report and Review of the Literature

Cited by 19 publications

References 35 publications

The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis

The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis

Clinical Management in Systemic Type Pseudohypoaldosteronism Due to <i>SCNN1B</i> Variant and Literature Review

An infantile case of pseudohypoaldosteronism type 1 (PHA1) caused by a novel mutation of <i>NR3C2</i>

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