Phenotypic variation of autosomal recessive pseudohypoaldosteronism type I: a case in point

Ahluwalia, Gunjeet Kala; Dasouki, Majed; Lennon, Angela

doi:10.1002/ccr3.129

Cited by 13 publications

(19 citation statements)

References 22 publications

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“…Inactivating mutations of genes encoding MR and ENaC prevent aldosterone exhibiting mineralocorticoid activity, thereby causing pseudohypoaldosteronism type 1 (PHA1) [1, 2]. PHA1 is a rare inherited disorder with an estimated incidence of 1:47,000 to 1:80,000, and a prevalence of <1/1,000,000 [3-5]. It was first described by Cheek and Perry [6] in a male neonate with severe salt wasting but with normal renal and adrenal functions.…”

Section: Introductionmentioning

confidence: 99%

“…The renal form is relatively mild and usually remits spontaneously during follow-up [3, 9]. The systemic form of PHA1 is characterized by defective sodium transport in numerous organ systems, including the kidneys, lungs, colon, sweat glands, and salivary glands [3, 5, 7, 10]. The systemic form is inherited in an autosomal recessive manner and is caused by loss-of-function mutations in the genes SCNN1A (sodium channel epithelial 1 alpha subunit, OMIM No.…”

Section: Introductionmentioning

confidence: 99%

“…600760), and SCNN1G (sodium channel epithelial 1 gamma subunit, OMIM No. 600761) that encode for the α-, β-, and γ-subunits of ENaC, respectively [3, 5, 7, 10, 11]. The ENaC is a heteromeric protein complex made up of α-, β-, and γ-subunits.…”

Section: Introductionmentioning

confidence: 99%

“…ENaCs are ubiquitous channels expressed in the kidneys and various extrarenal organs including the lungs, colon, salivary glands, and sweat glands. While ENaC regulates renal sodium reabsorption, thereby maintaining electrolyte homeostasis, in the lungs it primarily regulates the reabsorption of pulmonary interstitial fluid on the cell surface [1, 5, 7, 12]. …”

Section: Introductionmentioning

confidence: 99%

“…Patients with a systemic form of PHA1 have a more severe clinical phenotype with multi-organ involvement and usually require life-long sodium replacement [3, 5, 7, 10]. The majority of mutations detected in systemic PHA1 are nonsense, single-base deletions or insertions leading to frameshift or splice-site mutations that result in truncated ENaC channel subunit proteins.…”

Section: Introductionmentioning

confidence: 99%

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Systemic Pseudohypoaldosteronism Type 1 due to 3 Novel Mutations in SCNN1Aand SCNN1BGenes

et al. 2019

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Objective: The systemic form of pseudohypoaldosteronism type 1 (PHA1) is an autosomal recessive disorder characterized by defective sodium transport in multi-organ systems. Mutations in the genes encoding the amiloride-sensitive epithelial sodium channel, ENaC, account for genetic causes of systemic PHA1. We describe systemic PHA1 due to 4 novel variants detected in SCNN1A and SCNN1B in 3 cases from 3 unrelated consanguineous families. Patients and Methods: We evaluated the clinical presentations, biochemical and hormonal characteristics, and molecular genetic analysis results of 3 patients from 3 unrelated consanguineous families and parents from whom samples were available. Results: The ages at presentation were postnatal days 9, 10, and 5. The main presentation symptoms were vomiting, poor feeding, weakness, weight loss, and skin rash. All patients exhibited laboratory characteristics including severe hyponatremia, hyperkalemia, metabolic acidosis, elevated plasma renin, elevated aldosterone, and positive sweat tests, suggesting a diagnosis of systemic PHA1. Molecular genetic analysis revealed 2 novel pathogenic variants [c.87C>A(p.Tyr29*)/IVS9 + 1G>A (c.1346 + 1G>A)] in SCNN1Bin case 1, a novel homozygous pathogenic variant [p.His69Arg(c.206A>G] in SCNN1Ain case 2, and a homozygous one-base duplication, p.A200Gfs*6 (c.598dupG), in SCNN1A in case 3. Conclusion: PHA1 should be considered at differential diagnosis in patients presenting with hyponatremia, hyperkalemia, and metabolic acidosis. The cases in this report involving 4 novel variants will add valuable insights into the phenotype-genotype relationship and will expand the mutation database.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Systemic Pseudohypoaldosteronism Type 1 due to 3 Novel Mutations in SCNN1Aand SCNN1BGenes

et al. 2019

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Rare forms of genetic paediatric adrenal insufficiency: Excluding congenital adrenal hyperplasia

Hasenmajer

Ferrigno

Minnetti

et al. 2023

Rev Endocr Metab Disord

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Adrenal insufficiency (AI) is a severe endocrine disorder characterized by insufficient glucocorticoid (GC) and/or mineralocorticoid (MC) secretion by the adrenal glands, due to impaired adrenal function (primary adrenal insufficiency, PAI) or to insufficient adrenal stimulation by pituitary ACTH (secondary adrenal insufficiency, SAI) or tertiary adrenal insufficiency due to hypothalamic dysfunction. In this review, we describe rare genetic causes of PAI with isolated GC or combined GC and MC deficiencies and we also describe rare syndromes of isolated MC deficiency. In children, the most frequent cause of PAI is congenital adrenal hyperplasia (CAH), a group of adrenal disorders related to steroidogenic enzyme deficiencies, which will not be included in this review. Less frequently, several rare diseases can cause PAI, either affecting exclusively the adrenal glands or with systemic involvement. The diagnosis of these diseases is often challenging, due to the heterogeneity of their clinical presentation and to their rarity. Therefore, the current review aims to provide an overview on these rare genetic forms of paediatric PAI, offering a review of genetic and clinical features and a summary of diagnostic and therapeutic approaches, promoting awareness among practitioners, and favoring early diagnosis and optimal clinical management in suspect cases.

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Attenuated Amiloride-Sensitive Current and Augmented Calcium-Activated Chloride Current in Marsh Rice Rat (Oryzomys palustris) Airways

et al. 2019

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Summary Prolonged heat and sea salt aerosols pose a challenge for the mammalian airway, placing the protective airway surface liquid (ASL) at risk for desiccation. Thus, mammals inhabiting salt marshes might have acquired adaptations for ASL regulation. We studied the airways of the rice rat, a rodent that inhabits salt marshes. We discovered negligible Na + transport through the epithelial sodium channel (ENaC). In contrast, carbachol induced a large Cl − secretory current that was blocked by the calcium-activated chloride channel (CaCC) inhibitor CaCCinhi-A01. Decreased mRNA expression of α, β, and γ ENaC, and increased mRNA expression of the CaCC transmembrane member 16A, distinguished the rice rat airway. Rice rat airway cultures also secreted fluid in response to carbachol and displayed an exaggerated expansion of the ASL volume when challenged with 3.5% NaCl. These data suggest that the rice rat airway might possess unique ion transport adaptations to facilitate survival in the salt marsh environment.

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Phenotypic variation of autosomal recessive pseudohypoaldosteronism type I: a case in point

Cited by 13 publications

References 22 publications

Systemic Pseudohypoaldosteronism Type 1 due to 3 Novel Mutations in <b><i>SCNN1A</i></b>and <b><i>SCNN1B</i></b>Genes

Systemic Pseudohypoaldosteronism Type 1 due to 3 Novel Mutations in <b><i>SCNN1A</i></b>and <b><i>SCNN1B</i></b>Genes

Rare forms of genetic paediatric adrenal insufficiency: Excluding congenital adrenal hyperplasia

Attenuated Amiloride-Sensitive Current and Augmented Calcium-Activated Chloride Current in Marsh Rice Rat (Oryzomys palustris) Airways

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