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BMJ Case Reports Sep 2023Bartter's syndrome (BS) is a rare group of hereditary salt losing tubulopathies due to impairment of renal transport mechanism. Herein, we report a boy in early...
Bartter's syndrome (BS) is a rare group of hereditary salt losing tubulopathies due to impairment of renal transport mechanism. Herein, we report a boy in early childhood who was diagnosed to have infantile Bartter's syndrome. Laboratory investigations revealed hypokalaemia and metabolic alkalosis which was managed with oral potassium chloride supplementation. The inner ear showed no anatomical abnormalities. Sequential cochlear implantation was performed 4 months apart. Postoperative electrical stimulation yielded good response and a symmetric mapping. The patient was on regular audio-verbal therapy. Cognitive impairment improved over time. Bilateral cochlear implantation showed excellent auditory outcomes.
Topics: Humans; Male; Cochlear Implantation; Bartter Syndrome; Infant; Treatment Outcome; Child, Preschool
PubMed: 37751985
DOI: 10.1136/bcr-2022-254155 -
American Journal of Kidney Diseases :... Jan 2024
PubMed: 38129069
DOI: 10.1053/j.ajkd.2023.10.005 -
Clinical Journal of the American... May 2024Liddle syndrome was initially characterized by hypertension, hypokalemia, metabolic alkalosis, and suppressed plasma renin and aldosterone, resulting from...
BACKGROUND
Liddle syndrome was initially characterized by hypertension, hypokalemia, metabolic alkalosis, and suppressed plasma renin and aldosterone, resulting from gain-of-function variants in the epithelial Na + channel (ENaC). Efficient treatment with ENaC inhibitors is available, but the phenotypic spectrum of genetically confirmed Liddle syndrome is unknown, and some patients may remain undiagnosed and at risk of inefficient treatment. In this study, we used a reverse phenotyping approach to investigate the Liddle syndrome phenotypic spectrum and genotype-phenotype correlations.
METHODS
Pubmed, Embase, Scopus, and the Human Gene Mutation Database were searched for articles reporting Liddle syndrome variants. The genetic variants were systematically classified to identify patients with genetically confirmed Liddle syndrome. We identified 62 articles describing 45 unique variants within 86 Liddle syndrome families, and phenotypic data were pooled for 268 patients with confirmed Liddle syndrome.
RESULTS
The Liddle syndrome variants localized to exon 13 of SCNN1B and SCNN1G , disrupting the PPPxY motif critical for downregulating ENaC activity. Hypertension sensitive to ENaC inhibition was present in 97% of adults carrying Liddle syndrome variants while hypokalemia, metabolic alkalosis, and plasma renin and aldosterone suppression showed incomplete penetrance. In addition, 95% and 55% of patients had a family history of hypertension or cerebrovascular events, respectively. The genotype had minor phenotypic effects; however, probands compared with relatives showed significant phenotypic discrepancies consistent with selection bias for initial genetic screening.
CONCLUSIONS
Patients with genetically confirmed Liddle syndrome displayed a phenotypic spectrum, with ENaC-sensitive hypertension and family history of hypertension being the most common features. The phenotype seemed independent of the specific gene or variant type involved.
Topics: Humans; Liddle Syndrome; Epithelial Sodium Channels; Phenotype; Adult; Genetic Association Studies; Female; Male; Hypertension; Renin; Hypokalemia; Adolescent; Young Adult; Genetic Predisposition to Disease; Child; Mutation
PubMed: 38265765
DOI: 10.2215/CJN.0000000000000430 -
Journal of the International Society of... Dec 2023This study examined the effects of oral and topical (PR Lotion; Momentous) sodium bicarbonate (NaHCO) during a battery of team sport-specific exercise tests. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study examined the effects of oral and topical (PR Lotion; Momentous) sodium bicarbonate (NaHCO) during a battery of team sport-specific exercise tests.
METHOD
In a block randomized, crossover, double-blind, placebo-controlled design, 14 recreationally trained male team sport athletes performed a familiarization visit and three experimental trials receiving: (i) 0.3 g·kg body mass (BM) NaHCO in capsules + placebo lotion (SB-ORAL), (ii) placebo capsules +0.9036 g·kg BM PR Lotion (SB-LOTION), or (iii) placebo capsules + placebo lotion (PLA). Supplements were given ~120 min prior to the team sport-specific exercise tests: countermovement jumps (CMJ), 8 × 25 m repeated sprints and Yo-Yo Intermittent Recovery Level 2 (Yo-Yo IR2). Blood acid-base balance (pH, bicarbonate) and electrolytes (sodium, potassium) were measured throughout. Rating of perceived exertion (RPE) was recorded after each sprint and post-Yo-Yo IR2.
RESULTS
Distance covered during the Yo-Yo IR2 was 21% greater for SB-ORAL compared with PLA (+94 m; = 0.009, = 0.64) whereas performance was only 7% greater for SB-LOTION compared with PLA (480 ± 122 vs. 449 ± 110 m; = 0.084). Total completion time for the 8 × 25 m repeated sprint test was 1.9% faster for SB-ORAL compared with PLA (-0.61 s; = 0.020, = 0.38) and 2.0% faster for SB-LOTION compared with PLA (-0.64 s; = 0.036, = 0.34). CMJ performance was similar between treatments ( > 0.05). Blood acid-base balance and electrolytes were significantly improved for SB-ORAL compared with PLA, but no differences were observed for SB-LOTION. Compared to PLA, RPE was lower for SB-LOTION after the fifth ( = 0.036), sixth ( = 0.012), and eighth ( = 0.040) sprints and for SB-ORAL after the sixth ( = 0.039) sprint.
CONCLUSIONS
Oral NaHCO improved 8 × 25 m repeated sprint (~2%) and Yo-Yo IR2 performance (21%). Similar improvements in repeated sprint times were observed for topical NaHCO (~2%), but no significant benefits were reported for Yo-Yo IR2 distance or blood acid-base balance compared to PLA. These findings suggest that PR Lotion might not be an effective delivery system for transporting NaHCO molecules across the skin and into systematic circulation, therefore further research is needed to elucidate the physiological mechanisms responsible for the ergogenic effects of PR Lotion.
Topics: Humans; Male; Athletes; Athletic Performance; Double-Blind Method; Exercise Test; Polyesters; Running; Sodium Bicarbonate; Team Sports; Cross-Over Studies
PubMed: 37227399
DOI: 10.1080/15502783.2023.2216678 -
Clinical Research in Cardiology :... May 2024To determine the prevalence and the impact on prognosis of metabolic alkalosis (MA) in patients admitted for acute heart failure (AHF).
AIMS
To determine the prevalence and the impact on prognosis of metabolic alkalosis (MA) in patients admitted for acute heart failure (AHF).
METHODS AND RESULTS
The ALCALOTIC is a multicenter, observational cohort study that prospectively included patients admitted for AHF. Patients were classified into four groups according to their acid-base status on admission: acidosis, MA, respiratory alkalosis, and normal pH (reference group for comparison). Primary endpoint was all-cause in-hospital mortality, and secondary endpoints included 30/90-day all-cause mortality, all-cause readmission, and readmission for HF. Associations between endpoints and acid-base alterations were estimated in a multivariate Cox regression model including sex, age, comorbidities, and Barthel index and expressed as hazard ratio (HR) with 95% confidence interval (95% CI). Six hundred sixty-five patients were included (84 years and 57% women), and 40% had acid-base alterations on admission: 188 (28%) acidosis and 78 (12%) alkalosis. The prevalence (95% CI) of MA was 9% (6.8-11.2%). Patients with MA were more women; had fewer comorbidities, better renal function, and higher left ventricle ejection fraction values; and received more treatment with oral acetazolamide during hospitalization and at discharge. MA was not associated with a higher risk of in-hospital mortality and 30/90-day all-cause mortality or readmissions but was associated with a significant increase in readmissions for HF at 30 and 90 days (adjusted HR [95% CI] 3.294 [1.397-7.767], p = 0.006 and 2.314 [1.075-4.978], p = 0.032).
CONCLUSION
The prevalence of MA in patients admitted for AHF was 9%, and its presence was associated with more readmissions for HF but not with all-cause mortality.
PubMed: 38709335
DOI: 10.1007/s00392-024-02452-z -
Electrolyte & Blood Pressure : E & BP Dec 2023Pseudo-Bartter syndrome is a well-known differential diagnosis that needs to be excluded in cases of normotensive hypokalemic metabolic alkalosis. Pseudo-Bartter...
Pseudo-Bartter syndrome is a well-known differential diagnosis that needs to be excluded in cases of normotensive hypokalemic metabolic alkalosis. Pseudo-Bartter syndrome and pseudo-Gitelman syndrome are often collectively referred to as pseudo-Bartter/Gitelman syndrome; however, pseudo-Gitelman syndrome should be considered as a separate entity because Gitelman syndrome is characterized by hypocalciuria and hypomagnesemia, while Bartter syndrome is usually associated with hypercalciuria. Herein, we report the cases of two young adult female patients who presented with severe hypokalemic metabolic alkalosis, hypocalciuria, and hypomagnesemia. Diuretic or laxative abuse and self-induced vomiting were absent, and a chloride deficit and remarkable bicarbonaturia were observed. Initial sequencing studies for , , and revealed no mutations, and whole-exome sequencing revealed no pathogenic variants. The metabolic alkalosis was saline-responsive in one case, and steroid therapy was necessary in the other to relieve chronic tubulointerstitial nephritis, which was diagnosed with kidney biopsy. A new category of pseudo-Gitelman syndrome should be defined, and various etiologies should be investigated.
PubMed: 38152600
DOI: 10.5049/EBP.2023.21.2.72 -
The American Surgeon Sep 2023Hypertrophic Pyloric Stenosis (HPS) is a common surgical disease in infants. Traditionally, patients present with projectile emesis and severe dehydration with metabolic...
Hypertrophic Pyloric Stenosis (HPS) is a common surgical disease in infants. Traditionally, patients present with projectile emesis and severe dehydration with metabolic alkalosis. We looked to assess if patients presenting as a transfer vs directly to our facility as well as race affected patients' initial presentation and outcomes. We performed a retrospective analysis of 131 patients who presented to with a diagnosis of HPS from 2015 to 2021 assessing how transfer status and patient race affected presenting electrolyte levels and length of stay (LOS). We found no statistically significant difference in patients' presenting electrolyte levels and hospital LOS based on transfer status or patient race. We believe this reflects availability and widespread utility of ultrasound. We suggest that this could be used as a model for standardizing care to equalize outcomes in other pediatric diseases which currently show large disparities in care based on race and geographical location.
Topics: Infant; Child; Humans; Pyloric Stenosis, Hypertrophic; Retrospective Studies; Ultrasonography; Electrolytes
PubMed: 37157788
DOI: 10.1177/00031348231174008 -
Archives of Medical Research Sep 2023Bartter's syndrome (BS) is a group of salt-wasting tubulopathies characterized by hypokalemia, metabolic alkalosis, hypercalciuria, secondary hyperaldosteronism, and low...
BACKGROUND
Bartter's syndrome (BS) is a group of salt-wasting tubulopathies characterized by hypokalemia, metabolic alkalosis, hypercalciuria, secondary hyperaldosteronism, and low or normal blood pressure. Loss-of-function variants in genes encoding for five proteins expressed in the thick ascending limb of Henle in the nephron, produced different genetic types of BS.
AIM
Clinical and genetic analysis of families with Antenatal Bartter syndrome (ABS) and with Classic Bartter syndrome (CBS).
METHODS
Nine patients from unrelated non-consanguineous Mexican families were studied. Massive parallel sequencing of a gene panel or whole-exome sequencing was used to identify the causative gene.
RESULTS
Proband 1 was homozygous for the pathogenic variant p.Arg302Gln in the SLC12A1 gene encoding for the sodium-potassium-chloride NKCC2 cotransporter. Proband 3 was homozygous for the nonsense variant p.Cys308* in the KCNJ1 gene encoding for the ROMK potassium channel. Probands 7, 8, and 9 showed variants in the CLCKNB gene encoding the chloride channel ClC-Kb: proband 7 was compound heterozygous for the deletion of the entire gene and the missense change p.Arg438Cys; proband 8 presented a homozygous deletion of the whole gene and proband 9 was homozygous for the nonsense mutation p.Arg595*. A heterozygous variant of unknown significance was detected in the SLC12A1 gene in proband 2, and no variants were found in SLC12A1, KCNJ1, BSND, CLCNKA, CLCNKB, and MAGED2 genes in probands 4, 5, and 6.
CONCLUSIONS
Genetic analysis identified loss-of-function variants in the SLC12A1, KCNJ1, and CLCNKB genes in four patients with ABS and in the CLCNKB gene in two patients with CBS.
Topics: Humans; Female; Pregnancy; Bartter Syndrome; Homozygote; Sequence Deletion; Heterozygote; Mutation; Antigens, Neoplasm; Adaptor Proteins, Signal Transducing; Chloride Channels
PubMed: 37516009
DOI: 10.1016/j.arcmed.2023.102859 -
Diagnostics (Basel, Switzerland) Oct 2023Asphyxia, a leading cause of illness and death in newborns, can be improved by early detection and management. Arterial blood gas (ABG) analysis is commonly used to...
Asphyxia, a leading cause of illness and death in newborns, can be improved by early detection and management. Arterial blood gas (ABG) analysis is commonly used to diagnose and manage asphyxia, but it is invasive and carries risks. Dermal interstitial fluid (ISF) is an alternative physiological fluid that can provide valuable information about a person's health. ISF is more sensitive to severe hypoxia and metabolic disorders compared to blood, making it an attractive option for minimally invasive asphyxia detection using biosensors. However, obtaining ISF samples from humans is challenging due to ethical concerns and sampling difficulties. To address this, researchers are developing ISF-mimicking solutions as substitutes for early testing and evaluation of biosensors. This paper focuses on the development of these solutions for bench-based testing and validation of continuous asphyxia-monitoring biosensors. With an understanding of the factors influencing system quality and performance, these solutions can aid in the design of biosensors for in vivo monitoring of dermal ISF. Monitoring interstitial fluid pH levels can provide valuable insights into the severity and progression of asphyxia, aiding in accurate diagnosis and informed treatment decisions. In this study, buffer solutions were prepared to mimic the pH of ISF, and their electrical properties were analyzed. The results suggest that certain buffers can effectively mimic metabolic acidosis associated with asphyxia (pH < 7.30), while others can mimic metabolic alkalosis (pH > 7.45). Overall, this research contributes to the development of ISF-mimicking solutions and lays the groundwork for biosensor systems that monitor dermal ISF in real time.
PubMed: 37835868
DOI: 10.3390/diagnostics13193125 -
JFMS Open Reports 2023A 6-year-old female Siamese cat presented with an 8-week history of vomiting and progressive hyporexia. On presentation, the cat was found to have a hypochloremic...
CASE SUMMARY
A 6-year-old female Siamese cat presented with an 8-week history of vomiting and progressive hyporexia. On presentation, the cat was found to have a hypochloremic alkalosis. Imaging demonstrated hiatal hernia and megaesophagus. Exploratory laparotomy demonstrated a paraesophageal hiatal hernia. The hernia was reduced, phrenoplasty and esophagopexy were performed, and a gastrotomy tube was placed. Treatment of the hernia led to resolution of the megaesophagus.
RELEVANCE AND NOVEL INFORMATION
Megaesophagus can occur secondarily to paraesophageal hernia in the cat. In this case, correction of the paraesophageal hernia led to complete resolution of the esophageal dilation and all associated clinical signs.
PubMed: 37841898
DOI: 10.1177/20551169231199451