Pseudohypoaldosteronism Type 1: The Presentation and Management of a Neonate With a Novel Mutation of the SCNN1B Gene Found in Two Hispanic Siblings

Pugh, Charles Preston

doi:10.7759/cureus.23918

Cited by 4 publications

(5 citation statements)

References 9 publications

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“…Clusters of ethnic prevalence have been reported in the literature [16,17]. However, this is the first case report to present four neonates whose parents are of the same ethnicity, speaking a rarely known dialect called Mixteco, and now residing in the same geographic area in California.…”

Section: Typementioning

confidence: 77%

Autosomal Recessive Pseudo Hypoaldosteronism- Type 1 in Four Patients from Mixteco-Speaking Families from Coastal California

2024

Ann Case Report

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Pseudo hypoaldosteronism type 1 (PHA1) is a rare condition characterized by hyponatremia, hyperkalemia, metabolic acidosis, and elevated serum aldosterone. Severe electrolyte derangements occur in the setting of aldosterone resistance. Autosomal recessive PHA1 confers aldosterone resistance through defective sodium epithelial channels present in the kidneys, sweat glands, salivary glands, and colon attributing to the systemic nature of the condition. Infants with this condition develop severe hyperkalemia, hyponatremia, and metabolic acidosis in the neonatal period. We present four infants of Mixteco dialectspeaking Hispanic parents, presenting in the neonatal period with severe hyperkalemia and hyponatremia due to PHA1b.

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Section: Typementioning

confidence: 77%

Autosomal Recessive Pseudo Hypoaldosteronism- Type 1 in Four Patients from Mixteco-Speaking Families from Coastal California

2024

Ann Case Report

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“…Renal PHA 1 (PHA1a) is an autosomal dominant inherited disorder with a heterogeneous NR3C2 gene mutation characterized by an inactivating mutation [2,4]. This gene encodes for mineralocorticoid receptors that can result in the absence of binding the aldosterone to the receptor with a phenotypic expression restricted to the kidney [3,5].…”

Section: Discussionmentioning

confidence: 99%

“…The mortality rate is considered high during the neonatal period and often requires prolonged hospitalization [1]. Neonatal salt wasting can reduce the function of epithelium sodium channels secondary to variable sodium channel gene mutations, including SCNN1A, SCNN1B, and SCNN1G, which can pose a signi cant life-threatening sequela [2]. Studies showed that patients with the gene-structured disrupted mutation, including gross deletion, deletion with frameshift and truncation, and nonsense mutation, can interfere with the normal function of the encoded protein subunit of SCNN1A and tend to develop severe phenotype form of PHA at the onset of diagnosis with less improvement over-time.…”

Section: Discussionmentioning

confidence: 99%

“…Pseudohypoaldosteronism (PHA) was rst described by Cheek and Perry in 1958 as a rare aldosterone unresponsiveness that is characterized by multi-organ involvement affecting sodium salt wasting, poor renal excretion, and severe volume depletion resulting in hyponatremia, hyperkalaemia, and metabolic acidosis [1,2]. In such cases, it can be acquired.…”

Section: Introductionmentioning

confidence: 99%

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Clinical Manifestations of Pseudohypoaldosteronism with Genotype-phenotype Correlation. A Single Center Experience, A Retrospective Cohort Study.

Bin-Abbas,

Aljaser,

AlSagheir

et al. 2024

Preprint

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Background: Pseudohypoaldosteronism (PHA) is a rare endocrine disorder characterized by unresponsiveness, multi-organ involvement affecting sodium salt wasting, poor renal excretion, and severe volume depletion resulting in electrolyte imbalance (hyponatremia, hyperkalaemia, and metabolic acidosis) and further classified into type 1 and 2. Ali et al. reported that PHA1b geno-phenotype correlation has not been well described. As such, in our study, we propose how the clinical behaviour of this subtype can be predictable. Moreover, the diagnosis of any of the PHA types is made by the clinical presentation and laboratory findings during a clinical suspicion setting. Methods: A descriptive retrospective study includes 22 patients diagnosed with PHA during 2023 in the endocrine subdivision of paediatric service in KFSHRC. The informed consent was obtained from either the patients or their guardians. Results: Of a total of 22 patients, ages ranged between 3 days to 2 years at presentation, 95% of them presented with vomiting, 63.3% had respiratory symptoms, 50% had hypotension 31% had dermatitis, and 31% had polyurea, 27% had HTN, 22% had UTI only one patient had arrhythmia, none of them had gallstone. Labs were Lowest Na; 110–132 Lowest Cl: 81–108 Lowest HCO3: 10–18 Highest K: 5.5-8 Aldosterone: 7510 − 1659, half of the patient did not do Aldosterone level. Renin: 50–751 Number of admissions: range from 0 to 20 times. Treatment: NaCl dose range (2-480 meq/kg/day) NaHCO3 (1–34 meq/kg/day) Kayexalate (0.5–45 g/kg/day) One patient needed a gastrostomy tube. One patient was off treatment at the age of 6 years. Severity at presentation ranges from very severe to 4 severe, Then improved with age to range between very mild to moderate. Discussion: PHA1a has a heterogeneous inactivating mutation in the NR3C2 gene; it encodes for a mineralocorticoid receptor responsible for aldosterone binding. Therefore, mutations are associated with a phenotype restricted to the kidneys. As a course, this disease has an early life onset, which is almost always in the neonatal period, presenting with fever, feeding difficulties, nausea, vomiting, weight loss, recurrent pulmonary infection, and sudden cardiac arrest alongside laboratory findings in the form of electrolyte imbalance which includes hyponatremia, hyperkalaemia and salt wasting with elevated plasma renin and aldosterone levels. On the other hand, PHA1b is multi-systemic and mainly caused by mutations in the ENaC channel, affecting sodium reabsorption in the body. It manifests in the first week of life with electrolyte imbalance with nonspecific symptoms such as nausea and vomiting alongside hypotension, with salt-wasting episodes. It has been demonstrated that PHA1b usually presents with a more severe clinical phenotype than PHA1a. Furthermore, complications with the PHA1b subtype are more prone to develop. Conclusion: PHA is a rare genetic endocrine disorder that needs awareness by the endocrinologist of its existence. It is a clinical diagnosis that requires monitoring, follow-up, and close observation of affected patients. Hence, this is because pheno-genotype correlation is an expandable process in the endocrine medical literature. Our single-centre experience gives an insight into the predictable clinical behaviour of this under-diagnosed condition to improve further the physicians related to the paediatric population's understanding of the PHA natural course. Also, to have a better provisional plan and management care for affected individuals to increase the likelihood of a better prognosis further, better quality of life, and survival.

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“…The disease is caused by mutations in the genes SCNN1A [135,145,152,[272][273][274][275][276][277][278][279][280][281][282][283][284][285][286][287][288], SCNN1B [135,146,151,[272][273][274][275]284,285,[289][290][291][292][293][294][295][296][297] and SCNN1G [283,286,290,[298][299][300] encoding for the ENaC subunits (Tables S1-S3; Figures S1-S3 [38,301]). Mutations of ENaC causing PHA-1B result in reduced or complete loss of ENaC function, depending on the type of mutation.…”

Section: Pseudohypoaldosteronism Type 1 (Pha-1b)mentioning

confidence: 99%

The Epithelial Sodium Channel—An Underestimated Drug Target

Lemmens‐Gruber

Tzotzos²

2023

IJMS

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Epithelial sodium channels (ENaC) are part of a complex network of interacting biochemical pathways and as such are involved in several disease states. Dependent on site and type of mutation, gain- or loss-of-function generated symptoms occur which span from asymptomatic to life-threatening disorders such as Liddle syndrome, cystic fibrosis or generalized pseudohypoaldosteronism type 1. Variants of ENaC which are implicated in disease assist further understanding of their molecular mechanisms in order to create models for specific pharmacological targeting. Identification and characterization of ENaC modifiers not only furthers our basic understanding of how these regulatory processes interact, but also enables discovery of new therapeutic targets for the disease conditions caused by ENaC dysfunction. Numerous test compounds have revealed encouraging results in vitro and in animal models but less in clinical settings. The EMA- and FDA-designated orphan drug solnatide is currently being tested in phase 2 clinical trials in the setting of acute respiratory distress syndrome, and the NOX1/ NOX4 inhibitor setanaxib is undergoing clinical phase 2 and 3 trials for therapy of primary biliary cholangitis, liver stiffness, and carcinoma. The established ENaC blocker amiloride is mainly used as an add-on drug in the therapy of resistant hypertension and is being studied in ongoing clinical phase 3 and 4 trials for special applications. This review focuses on discussing some recent developments in the search for novel therapeutic agents.

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Pseudohypoaldosteronism Type 1: The Presentation and Management of a Neonate With a Novel Mutation of the SCNN1B Gene Found in Two Hispanic Siblings

Cited by 4 publications

References 9 publications

Autosomal Recessive Pseudo Hypoaldosteronism- Type 1 in Four Patients from Mixteco-Speaking Families from Coastal California

Autosomal Recessive Pseudo Hypoaldosteronism- Type 1 in Four Patients from Mixteco-Speaking Families from Coastal California

Clinical Manifestations of Pseudohypoaldosteronism with Genotype-phenotype Correlation. A Single Center Experience, A Retrospective Cohort Study.

The Epithelial Sodium Channel—An Underestimated Drug Target

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