Clinical Management in Systemic Type Pseudohypoaldosteronism Due to SCNN1B Variant and Literature Review
Ontology highlight
ABSTRACT:
SUBMITTER: Karacan Kucukali G
PROVIDER: S-EPMC8638636 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:UnlabelledAutosomal recessive pseudohypoaldosteronism type 1 (PHA1) is a rare disorder characterized by sodium wasting, failure to thrive, hyperkalemia, hypovolemia and metabolic acidosis. It is due to mutations in the amiloride-sensitive epithelial sodium channel (ENaC) and is characterized by diminished response to aldosterone. Patients may present with life-threatening hyperkalemia, which must be recognized and appropriately treated. A 32-year-old female was referred to the National Institutes of Health (NIH) for evaluation of hyperkalemia and muscle pain. Her condition started in the second week of life, when she was brought to an outside hospital lethargic and unresponsive. At that time, she was hypovolemic, hyperkalemic and acidotic, and was eventually treated with sodium bicarbonate and potassium chelation. At the time of the presentation to the NIH, her laboratory evaluation revealed serum potassium 5.1 mmol/l (reference range: 3.4-5.1 mmol/l), aldosterone 2800 ng/dl (reference range: ≤21 ng/dl) and plasma renin activity 90 ng/ml/h (reference range: 0.6-4.3 ng/ml per h). Diagnosis of PHA1 was suspected. Sequencing of the SCNN1B gene, which codes for ENaC, revealed that the patient is a compound heterozygote for two novel variants (c.1288delC and c.1466+1 G>A), confirming the suspected diagnosis of PHA1. In conclusion, we report a patient with novel variants of the SCNN1B gene causing PHA1 with persistent, symptomatic hyperkalemia.Learning pointsPHA1 is a rare genetic condition, causing functional abnormalities of the amiloride-sensitive ENaC.PHA1 was caused by previously unreported SCNN1B gene mutations (c.1288delC and c.1466+1 G>A).Early recognition of this condition and adherence to symptomatic therapy is important, as the electrolyte abnormalities found may lead to severe dehydration, cardiac arrhythmias and even death.High doses of sodium polystyrene sulfonate, sodium chloride and sodium bicarbonate are required for symptomatic treatment.
| S-EPMC4722246 | biostudies-literature
Project description:Pseudohypoaldosteronism type 1 (PHA-1, MIM #264350) is caused by defective transepithelial sodium transport. Affected patients develop life-threatening neonatal-onset salt loss, hyperkalemia, acidosis, and elevated aldosterone levels due to end-organ resistance to aldosterone. In this report, we present a patient diagnosed as PHA-1 who had clinical and laboratory findings compatible with the diagnosis and had genetically proven autosomal recessive PHA-1. The patient received high doses of sodium supplementation and potassium-lowering therapies; however, several difficulties were encountered in the management of this case. The aim of this presentation was to point out the potential pitfalls in the treatment of such patients in the clinical practice and to recommend solutions.
| S-EPMC3119449 | biostudies-literature
Project description:Pseudohypoaldosteronism (PHA) type 1 is a disease showing mineralocorticoid resistance in the kidney and/or other mineralocorticoid target tissues. Patients with PHA1 present very high plasma aldosterone and renin levels, but they develop excessive salt wasting. There are three types of PHA1. The systemic form of PHA1 is inherited in an autosomal recessive manner and causes severe life-long salt loss in multiple target tissues, such as sweat glands, salivary glands, the colonic epithelium, and the lung. In the systemic form of PHA1, life-long salt supplementation is necessary. The second type is the renal form, where aldosterone resistance is shown only in the kidney, and its inheritance is autosomal dominant. In the renal form of PHA1, salt supplementation generally becomes unnecessary by 1-3 yr of age. The third type is the secondary PHA1, which is strongly associated with urinary tract infections and/or urinary tract malformations. This review summarizes the clinical features and molecular basis of PHA1. Understanding of its pathogenesis can be helpful for the early diagnosis and clinical care of affected children with PHA1.
| S-EPMC5537208 | biostudies-other
Project description:Systemic corticosteroid use to manage uncontrolled asthma and its associated healthcare burden may account for important health-related adverse effects. We conducted a systematic literature review to investigate the real-world extent and burden of systemic corticosteroid use in asthma. We searched MEDLINE and Embase databases to identify English-language articles published in 2010-2017, using search terms for asthma with keywords for oral corticosteroids and systemic corticosteroids. Observational studies, prescription database analyses, economic analyses, and surveys on oral/systemic corticosteroid use in children (>5 yr old), adolescents (12-17 yr old), and adults with asthma were included. We identified and reviewed 387 full-text articles, and our review included data from 139 studies. The included studies were conducted in Europe, North America, and Asia. Overall, oral/systemic corticosteroids were commonly used for asthma management and were more frequently used in patients with severe asthma than in those with milder disease. Long-term oral/systemic corticosteroid use was, in general, less frequent than short-term use. Compared with no use, long-term and repeated short-term oral/systemic corticosteroid use were associated with an increased risk of acute and chronic adverse events, even when doses were comparatively low. Greater oral/systemic corticosteroid exposure was also associated with increased costs and healthcare resource use. This review provides a comprehensive overview of oral/systemic corticosteroid use and associated adverse events for patients with all degrees of asthma severity and exposure duration. We report that oral/systemic corticosteroid use is prevalent in asthma management, and the risks of acute and chronic complications increase with the cumulative oral corticosteroid dosage.
| S-EPMC6999108 | biostudies-literature
Project description:BackgroundPseudohypoaldosteronism (PHA) diseases are difficult to diagnose because symptoms are often non-specific and an in-depth pathogenesis study is still lacking.Case presentationWe present the case of a 19-day-old neonate who presented with unexplained recurrent hyperkalaemia, hypovolemia and metabolic acidosis, whose parents did not have significant clinical disease characteristics. Whole-exome sequencing was performed to confirm the disease and genetic pattern of the neonate. Sanger sequencing was performed to identify the mutation sites. Secondary structure comparisons and 3D model construction were used to predict changes in protein structure. Two novel frameshift mutations in the SCNN1B gene were identified (c.1290delA and c.1348_1361del), which resulted in amino acid synthesis termination (p.Gln431ArgfsTer2 and p.Thr451AspfsTer6). Considering the clinical phenotype and genetic analysis, this case was finally identified as a PHA type I disease. Genetic analysis showed that the neonate suffered complex heterozygosity in the SCNN1B gene inherited from the parents, which is passed on in an autosomal recessive inheritance pattern. These two deleterious mutations resulted in an incomplete protein 3D structure.ConclusionsOur results have confirmed the associations of mutations in the SCNN1B gene with recurrent hyperkalaemia, which can cause severe PHA type I disease, meanwhile suggested clinical attention should be paid when persistent recurrent hyperkalemia is accompanied by these types of mutations.
| S-EPMC8960372 | biostudies-literature
Project description:BackgroundCutis laxa (CL) is a group of rare connective tissue disorders mainly characterized by wrinkled, redundant, inelastic, and sagging skin. Besides skin anomalies, in most CL forms multiple organs are involved, leading to severe multisystem disorders involving skeletal, cardiovascular, pulmonary, and central nervous systems. CL might be challenging to diagnose because of its different inheritance patterns, extensive phenotypic variability, and genetic heterogeneity. Herein, we report the clinical and molecular characterization of an 18-month-old infant with signs suggestive of recessive cutis laxa type 1C (ARCL1C), although with a relatively mild presentation.MethodsTo confirm the clinical suspicion, mutational screening of all the exons and intron-flanking regions of the latent transforming growth factor-beta binding protein 4 gene (LTBP4) was performed by Sanger sequencing on an ABI3130XL Genetic Analyzer.ResultsApart from the presence of the dermatological hallmark, the reported patient did not show pulmonary emphysema, which is the most common and discriminative finding of ARCL1C together with gastrointestinal and urinary involvement. Indeed, pulmonary involvement only included episodes of respiratory distress and diaphragmatic eventration; intestinal dilation and tortuosity and hydronephrosis were also present. Molecular analysis disclosed the novel homozygous c.1450del (p.Arg484Glyfs*290) pathogenic variant in exon 12 of LTBP4, thus leading to the diagnosis of ARCL1C.ConclusionOur findings expand both the knowledge of the clinical phenotype and the allelic repertoire of ARCL1C. The comparison of the patient's features with those of the other patients reported up to now offers future perspectives for clinical research in this field.
| S-EPMC6625097 | biostudies-literature
Project description:PURPOSE:Over 150,000 variants have been reported to cause Mendelian disease in the medical literature. It is still difficult to leverage this knowledge base in clinical practice, as many reports lack strong statistical evidence or may include false associations. Clinical laboratories assess whether these variants (along with newly observed variants that are adjacent to these published ones) underlie clinical disorders. METHODS:We investigated whether citation data-including journal impact factor and the number of cited variants (NCV) in each gene with published disease associations-can be used to improve variant assessment. RESULTS:Surprisingly, we found that impact factor is not predictive of pathogenicity, but the NCV score for each gene can provide statistical support for prediction of pathogenicity. When this gene-level citation metric is combined with variant-level evolutionary conservation and structural features, classification accuracy reaches 89.5%. Further, variants identified in clinical exome sequencing cases have higher NCVs than do simulated rare variants from the Exome Aggregation Consortium database within the same set of genes and functional consequences (P?<?2.22? × ?10-16). CONCLUSION:Aggregate citation data can complement existing variant-based predictive algorithms, and can boost their performance without the need to access and review large numbers of papers. The NCV is a slow-growing metric of scientific knowledge about each gene's association with disease.
| S-EPMC6070443 | biostudies-literature
Project description:Generalized verrucosis (GV) is a group of immunodeficiency disorders accompanied by widespread human papillomavirus infection. We revisit two cases of GV due to congenital interleukin-7 deficiency successfully treated with systemic retinoids. We also present a review of the literature on the use of systemic retinoids to treat GV. Our review suggests that systemic retinoids are a safe and effective option for managing recalcitrant wart lesions in cases of GV.
| S-EPMC10048204 | biostudies-literature
Project description:ObjectivesWe aimed to investigate the efficacy of lifestyle interventions for the management of SSc.MethodsWe searched the MEDLINE, Embase, Web of Science and CINAHL databases in June 2021. We included studies conducted on five or more patients with SSc published between 1 January 2000 and the search date evaluating lifestyle interventions, excluding systematic reviews without meta-analyses. Critical appraisal was conducted using critical appraisal tools from the Joanna Briggs Institute. Thirty-six studies were included for full-text evaluation.ResultsA total of 17 studies evaluated the effect of physical exercise alone, whereas 14 studies evaluated educational interventions for mental health management, often with physical exercise as a central component. At an aggregated level, these studies support patient education and physical exercise for the improvement of physical function, in particular hand and mouth function. Studies on diet and nutrition were few (n = 5) and pertained to gastrointestinal as well as anthropometric outcomes; these studies were insufficient to support any conclusions.ConclusionPhysical exercise and patient education should be considered for improving physical function in patients with SSc. These interventions can be provided alongside pharmacotherapy, but there is no evidence supporting that they can be a substitute. Further research should aim at assessing the effects of reductions of harmful exposures, including tobacco smoking and alcohol, improving sleep and enhancing social relations, three hitherto underexplored facets of lifestyle in the context of SSc.
| S-EPMC11001494 | biostudies-literature
Project description:Large-scale transcriptome and methylome data analyses obtained by high-throughput technologies have been enabling the identification of novel imprinted genes. We investigated genome-wide DNA methylation patterns in multiple human tissues, using a high-resolution microarray to uncover hemimethylated CpGs located in promoters overlapping CpG islands, aiming to identify novel candidate imprinted genes. Using our approach, we recovered ~30% of the known human imprinted genes, further 168 candidates were identified, 61 of which with at least three hemimethylated CpGs shared by more than two tissue types. Thirty-four of these candidate genes are members of the protocadherins cluster on 5q31.3; in mice, protocadherin genes have non-imprinted monoallelic randomic expression, which might be the case in humans. Among the remaining 27 genes, ZNF331 was recently validated as an imprinted gene, and six of them have been reported as candidates, supporting our prediction. Five candidates (CCDC166, ARC, PLEC, TONSL and VPS28) map to 8q24.3, and might constitute a novel imprinted cluster. Additionally, we performed a comprehensive compilation of known human and mice imprinted genes from literature and databases, and a comparison among high-throughput imprinting studies in humans. The screening for hemimethylated CpGs shared by multiple human tissues, together with the extensive review, appears as a useful approach to reveal candidate imprinted genes.
2017-09-26 | GSE103413 | GEO