Hypokalemic Metabolic Alkalosis Research Articles

Ectopic cushing's syndrome: delayed recognition of a rare but sinister cause of hypokalaemic metabolic alkalosis

Ectopic cushing's syndrome: delayed recognition of a rare but sinister cause of hypokalaemic metabolic alkalosis

Acquired Bartter-like syndrome associated with colistin use in an adult patient: a case report.

Colistin is an effective antibiotic utilized for the treatment of Gram-negative bacterial infections with coverage against a broad spectrum of bacteria. Despite the broad antibacterial coverage, this antibiotic can have serious complications such as acute kidney injury. Colistin also can have a toxic effect on the loop of Henle, causing tubulopathy, electrolyte imbalances, and the occurrence of Bartter-like syndrome (BLS) which is characterized by magnesium and calcium disturbances, polyuria, and metabolic alkalosis. We here report a 32-year-old male with a history of multiple trauma due to an accident that received colistin therapy for Pseudomonas isolation from wound culture on the 5th day of hospitalization. Polyuria, hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalcemia were developed on the first week of colistin administration. The patient received colistin until the 21st day of hospitalization. Serum calcium and magnesium levels became normal 1 day after stopping colistin, while urine volume and metabolic alkalosis resolved 6 days after colistin discontinuing. Therefore, it is crucial to adjust the dose of colistin to minimize its toxicity.

A Rare Case of Apparent Mineralocorticoid Excess Presenting as Endocrine Hypertension

A 3-year-old boy presented with polyuria and polydipsia for 18 months, along with growth failure. He was born prematurely, at 34 weeks of gestation, with a low birth weight. On examination, the child was severely underweight and hypertensive. Clinical history and evaluation could not identify any secondary causes of hypertension. There was no significant family history. An endocrine workup was planned, considering hypokalemia and metabolic alkalosis. This demonstrated hyporeninemic hypoaldosteronism and raised the possibility of apparent mineralocorticoid excess (AME) and Liddle syndrome. Clinical exome sequence analysis of HSD11B2 revealed a homozygous mutation in exon 5 (911A>G; p.His304Arg), which resulted in a missense mutation that confirmed the diagnosis of AME. A novel homozygous variant was found in the HSD11B2 gene in a subject with early onset hypertension associated with hypokalemic metabolic alkalosis, establishing the diagnosis of AME.

Hyponatremia: A Rare Complication of Gitelmans's Syndrome - Literature Review and Clinical Case

Abstract Gitelman's syndrome (GS) is a variant of classical Bartter's syndrome (BS) in adults characterized by hypokalemic metabolic alkalosis, hypocalciuria (daily excretion <2.0 mg/kg body weight), hypomagnesaemia (<1.5 mg/dl), together with a normal to low blood pressure. In 1996, Simon et al. reported complete linkage between the syndrome and the thiazide-sensitive sodium chloride coporter (TSC) on chromosome 16q13 (Human Gene Mapping Workshop-approved symbol: SLCA3). Other metabolic features of GS include normonatremia, hyperuricemia, normocalcemia, increased plasma renin and aldosterone/potassium ratio, and inappropriately high renal potassium, magnesium, and chloride excretion. In this paper, we describe two affected patients who developed severe hyponatremia and hypouricemia. To the best of our knowledge, this complication has not been described previously.

Bartter Syndrome: A Systematic Review of Case Reports and Case Series.

Background and Objectives: Bartter syndrome (BS) is a rare group of autosomal-recessive disorders that usually presents with hypokalemic metabolic alkalosis, occasionally with hyponatremia and hypochloremia. The clinical presentation of BS is heterogeneous, with a wide variety of genetic variants. The aim of this systematic review was to examine the available literature and provide an overview of the case reports and case series on BS. Materials and Methods: Case reports/series published from April 2012 to April 2022 were searched through Pubmed, JSTOR, Cochrane, ScienceDirect, and DOAJ. Subsequently, the information was extracted in order to characterize the clinical presentation, laboratory results, treatment options, and follow-up of the patients with BS. Results: Overall, 118 patients, 48 case reports, and 9 case series (n = 70) were identified. Out of these, the majority of patients were male (n = 68). A total of 21 patients were born from consanguineous marriages. Most cases were reported from Asia (73.72%) and Europe (15.25%). In total, 100 BS patients displayed the genetic variants, with most of these being reported as Type III (n = 59), followed by Type II (n = 19), Type I (n = 14), Type IV (n = 7), and only 1 as Type V. The most common symptoms included polyuria, polydipsia, vomiting, and dehydration. Some of the commonly used treatments were indomethacin, potassium chloride supplements, and spironolactone. The length of the follow-up time varied from 1 month to 14 years. Conclusions: Our systematic review was able to summarize the clinical characteristics, presentation, and treatment plans of BS patients. The findings from this review can be effectively applied in the diagnosis and patient management of individuals with BS, rendering it a valuable resource for nephrologists in their routine clinical practice.

Genotypic variability in patients with clinical diagnosis of Bartter syndrome type 3

Bartter syndrome (BS) is a salt-losing hereditary tubulopathy characterized by hypokalemic metabolic alkalosis with secondary hyperaldosteronism. Confirmatory molecular diagnosis may be difficult due to genetic heterogeneity and overlapping of clinical symptoms. The aim of our study was to describe the different molecular findings in patients with a clinical diagnosis of classic BS. We included 27 patients (26 families) with no identified pathogenic variants in CLCNKB. We used a customized Ion AmpliSeq Next-Generation Sequencing panel including 44 genes related to renal tubulopathies. We detected pathogenic or likely pathogenic variants in 12 patients (44%), reaching a conclusive genetic diagnosis. Variants in SLC12A3 were found in 6 (Gitelman syndrome). Median age at diagnosis was 14.6 years (range 0.1–31), with no history of prematurity or polyhydramnios. Serum magnesium level was low in 2 patients (33%) but urinary calcium excretion was normal or low in all, with no nephrocalcinosis. Variants in SLC12A1 were found in 3 (BS type 1); and in KCNJ1 in 1 (BS type 2). These patients had a history of polyhydramnios in 3 (75%), and the mean gestational age was 34.2 weeks (SD 1.7). The median age at diagnosis was 1.8 years (range 0.1–6). Chronic kidney disease and nephrocalcinosis were present in 1 (25%) and 3 (75%) patients, respectively. A variant in CLCN5 was found in one patient (Dent disease), and in NR3C2 in another patient (Geller syndrome). Genetic diagnosis of BS is heterogeneous as different tubulopathies can present with a similar clinical picture. The use of gene panels in these diseases becomes more efficient than the study gene by gene with Sanger sequencing.

34-year-old female with acute onset quadriparesis and recurrent carpopedal spasm

Gitelman syndrome is an autosomal recessive condition also characterized by hypokalemic metabolic alkalosis, with hypocalciuria and hypomagnesemia

#2640 SINGLE TUBULE RNASEQ FROM GITLEMAN SYNDROME MICE REVEALING MAGNESIUM HANDLING IN DISTAL RENAL TUBULES

Abstract Background and Aims Gitelman syndrome (GS) is characterized by salt-losing hypotension, hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria caused by a specific mutation in the thiazide-sensitive sodium chloride co-transporter (NCC) gene SLC12A3. However, magnesium (Mg2+) associated gene in the distal renal tubules remains unclear. Method We performed small samples RNA-seq from manual microdissection of distal convoluted tubules (DCT1s) in nonsense Ncc Ser707X (S707X) homozygous knockin mice (NccS707X/S707X mice) (n = 4) and wild-type (WT, n = 4). Cortical thick ascending limbs of Henle (cTALs), connecting tubule (CNT), cortical collecting duct (CCD) were also microdissected. Results Among DCT makers, Slc12a3 (NCC) and Pvalb (Parabumin) were significantly downregulated (Log2TPMS707X/WT: −4.45, P = 0.0003; −6.888258295, P = 0.0003, respectively). Mg2+ transporters of Trpm6 gene expression were significantly downregulated. In addition, Egf and Cnnm2 have been reported to increase TRPM6 trafficking or activity, were also decreased in DCT segment. Rack1 was also decreased in DCT1. Claudins including Cldn10, Cldn16, and Cldn19, involving paracellularly reabsorption of Ca2+and Mg2+, were not changed in cTALs. All findings indicate chronic hypokalemia may mediate DCT1 remodeling and affect development. Conclusion Our small samples RNA-Seq from dissected DCT highlight the possible molecular pathway of hypomagnesemia in GS. Chronic hypokalemia caused by inactivation of Slc12A3 gene may affect the DCT development causing loss of Mg2+ associated transporters.

Novel Intronic Mutations of the SLC12A3 Gene in Patients with Gitelman Syndrome.

Mutations in the SLC12A3 gene have been reported to cause Gitelman syndrome (GS), characterized by hypokalemic metabolic alkalosis. The aim of this research is to investigate the genetic mutations and clinical features of patients with clinical suspicion of GS. Six families were enrolled. The symptoms, clinical examination, laboratory results, genotypes, and effect of mutations on mRNA splicing were analyzed. Genomic DNA was screened for gene variations using whole exome sequence and Sanger sequencing. DNA sequences were compared with reference sequences. Genetic analysis revealed nine genetic variants of SLC12A3, including three novel heterozygous mutations (c.1096-2A>G, c.1862A>G, and c.2747+4del) and six previously characterized mutations (c.965-1_976delinsACCGAAAATTTT, c.506-1G>A, c.602-16G>A, c.533C >T, c.1456 G>A, and c.1108 G>C). Probands presented with the clinical syndrome of hypokalemia, increased plasma renin, hypocalciuria and hypokalemic alkalosis. These clinical manifestations and genotypes were consistent with the diagnostic criteria of GS. The study described the phenotypes and genotypes of six pedigrees involving GS patients, demonstrating the importance of SLC12A3 gene screening for GS. This study expands the mutation spectrum of SLC12A3 gene in GS.

Abstract #1411492: Loss-of-Function EGFR Mutation in Bartter Syndrome with Neonatal Epithelial Autoinflammation

Bartter syndrome (BS) manifests as hypokalemic and hypochloremic metabolic alkalosis and hyperreninemic hyperaldosteronism. Loss-of-function (LoF) mutations in any of seven genes cause different subtypes of BS. We sought the genetic cause of BS in a 17-year-old patient who presented with progressive nephrocalcinosis, hypercalciuria, polyuria, metabolic alkalosis, hypokalemia, significantly high urine chloride, failure-to-thrive, hypergammaglobulinemia, abnormal cerebral white matter signal changes, autoinflammation, and moderate intellectual disability. No mutations were identified in previously BS-associated genes in this patient with consanguineous parents, and all seven genes resided outside of genomic regions of homozygosity (ROH). Instead, whole-exome sequencing and homozygosity mapping identified a homozygous intronic mutation, c.2702-2A >G, in the epidermal growth factor receptor (EGFR) gene within an ROH of ∼28 Mb in chromosome 7p. Examination of the patient's RNA by RNA-Seq and RT-PCR confirmed the pathogenicity of this variant, causing aberrant splicing resulting in an in-frame retention of 27 nucleotides of intron 22 of EGFR. Immunofluorescence of proband's skin, with a monoclonal antibody, revealed reduced protein level of EGFR, instead of complete protein absence, presumably justifying the life compatibility of this mutation. Previously, three loss-of-function EGFR mutations have been reported in patients with neonatal lethal inflammatory skin lesions and bowel disease. Thus, these observations provide an association of an autosomal recessive BS with hypomorphic EGFR mutation, expanding the phenotypic spectrum of the EGFR-associated disorders.

Hypertension with Hypokalemic Metabolic Alkalosis: The Diagnosis Is Apparent.

Rush University Medical Center Chicago, Illinois acorresponding author: Roger Rodby, M.D., FACP, FASN: [email protected]

Gitelman Syndrome – A Case Report

Hypokalaemia is an electrolyte disorder, commonly encountered in clinical practice. Sometimes, it may present with severe life-threatening complications. We present here a case of 22-year-old female, who was admitted to intensive care unit, for severe hypokalaemia associated with cardiac and neurological complications. She had recurrence of such episodes. On detailed clinical and biochemical evaluation, she was diagnosed to have Gitelman syndrome (GS). She was treated with intravenous potassium and magnesium supplementation under cardiac monitoring and other supportive management. She was discharged in stable condition, on oral supplements, and remained stable on follow-up visits. GS is an autosomal recessive and renal tubular disorder characterised by hypokalaemic metabolic alkalosis with hypomagnesaemia, hypocalciuria, secondary hyperreninemic aldosteronism and hypotension. The disease is caused by biallelic inactivating mutations within the SLC12A3 gene encoding the thiazide-sensitive sodium chloride cotransporter expressed within the apical membrane of cells, lining the distal convoluted tubule. Since GS is an autosomal recessive trait, the recurrence risk for people with an affected child is 25%. It is very important to completely evaluate a patient with hypokalaemia to find the underlying cause. There can be various etiological factors for hypokalaemia ranging from common to rare disorders. If underlying aetiology remains undiagnosed, there may be recurrence as well as increased morbidity and mortality. GS is one such disorder, which needs prompt diagnostic evaluation and treatment.

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

Novel SLC12A3 gene mutations and clinical characteristics in two pedigrees with Gitelman syndrome.

Gitelman syndrome (GS) is an autosomal recessive tubulopathy resulting from inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). To date, more than 500 mutations have been identified in the SLC12A3 gene. In this study, we identified two new mutations in the SLC12A3 gene in two Chinese GS pedigrees. The clinical characteristics and laboratory examination of two suspected GS patients in our hospital were analyzed. In addition, two pedigrees including 11 members and 2 patients underwent SLC12A3 gene analysis. Both patients were middle-aged women with characteristics of hypokalemic metabolic alkalosis, hypomagnesemia, low level of urinary calcium and the elevated levels of renin-angiotensin-aldosterone system. So, they were clinically diagnosed as GS. Patient 2 also had type 2 diabetes and Graves'disease. Both patients were found to carry two mutations of SLC12A3 gene by Sanger direct sequencing, which were all compound heterozygous mutations. We identified three mutations in these two Chinese GS pedigrees, one of which was c.179C>T (Thr60Met). The novel c.2159G>T (p. Gly720Val) and c.2675T>C (p. Leu892Pro) mutations were strongly predicted to be pathogenic using four network programs-Polyphen-2, SIFT, Mutation Taster and LRT. We identified two novel SLC12A3 genetic variant [c.2159G>T (p.Gly720Val) and c.2675T>C (p.Leu892Pro)] in two Chinese GS pedigrees. The discovery of new mutations has enriched the spectrum of SLC12A3 genotypes.

GITELMAN SYNDROME PRESENTING AS ACUTE RECURRENT HYPOKALEMIA

Gitelman Syndrome is also referred to as familial hypokalemia hypomagnesemia.It is characterised by Hypokalemic metabolic alkalosis in combination with hypomagnesemia and low urinary calcium excretion.Gitelman syndrome is transferred as an autosomal recessive trait.Most cases are diagnosed during adolescence or adulthood.We presented the case of 23year old male with no co-morbidities who presented to casualty with persistent recurrent hypokalemia. There was no history of drugs taken (even potassium supplements).

Diagnostic Accuracy of Acid-Base Status in Infants with Hypertrophic Pyloric Stenosis.

Hypertrophic pyloric stenosis is a condition in newborns in which the hypertrophic pyloric muscle causes gastric obstructive symptoms of progressive vomiting leading to hypochloremic hypokalemic metabolic alkalosis. The main aim of the research was to assess whether, based on the acid-base status, we can distinguish newborns who vomit due to pylorostenosis, compared with newborns who vomit for other unspecific reasons. The electronic records of patients in the hospital information system treated under the diagnosis Q40.0 (Congenital hypertrophic pyloric stenosis) (n = 69/included in the study = 53) in the period from 1 January 2014 to 1 January 2022 were reviewed retrospectively. For the purposes of the control group, the electronic records of patients treated in the emergency department with a diagnosis of R11.0 (Nausea and vomiting) (n = 53) without an established cause were randomly reviewed. In addition to the main aim, other research outcomes were to determine differences between groups in the following variables: duration of symptoms, family history, birth (preterm, term, post-term), birth weight, weight during examination, difference between birth weight and weight during an examination, type of vomiting, the thickness of the muscle wall and its length, and to calculate whether there is a correlation between the thickness and length of the pylorus muscle and the duration of vomiting in relation to variables from acid-base status. In relation to the variables of interest between the groups, statistically significant differences were observed in the duration of symptoms (Mdn 4 vs. 2 days, p = 0.002), weight at examination (Mean 3880 vs. 4439 g, p = 0.001), difference in weight between birth and examination (Mean 374 vs. 1010 g, p < 0.0001), and type of vomiting (explosive 45 vs. 22, p = 0.023). In the acid-base status between the groups, a statistically significant difference was recorded for pH (Mdn 7.457 vs. 7.422, p < 0.0001), bicarbonate (Mdn 25 vs. 23 mmol/L, p = 0.000), total carbon dioxide (Mdn 25 vs. 24 mmol/L, p = 0.011), base excess (Mdn 0.8 vs. -1.3 mmol/L, p = 0.000), potassium (Mdn 5 vs. 5.3 mmol/L, p = 0.006), ionized calcium (Mdn 1.28 vs. 1.31 mmol/L, p = 0.011), and glucose (Mdn 4.5 vs. 4.9 mmol/L, p = 0.007). Regardless of the group, the correlations between the duration of vomiting (r = 0.316, p = 0.021 vs. r = 0.148, p = 0.290) and the thickness (r = 0.190, p = 0.172) and length (r = 0.142, p = 0.311) of the pylorus muscle in relation to pH did not exist or were weak. In a world where radiological methods are not equally available everywhere, with promising acid-base indicators, prospective multicenter studies and meta-analyses must be pursued in the future in order not to miss the possible much greater diagnostic potential of acid-base status.

Hypercalcemia-induced hypokalemic metabolic alkalosis with hypophosphatemia in a multiple myeloma patient: lessons for the clinical nephrologist.

Hypercalcemia-induced hypokalemic metabolic alkalosis with hypophosphatemia in a multiple myeloma patient: lessons for the clinical nephrologist.

Pyloric Stenosis

Key Points Pyloric stenosis (PS) is characterized by abnormal hypertrophy of the antropyloric muscles, which can progress to gastric outlet obstruction leading to forceful vomiting, dehydration, and hypochloremic, hypokalemic metabolic alkalosis. Precise etiology is unclear, but risk factors include male sex, preterm birth, maternal smoking, family history of PS (especially in the mother), and early postnatal exposure to macrolides. Most commonly presents in newborns and infants 3 to 6 weeks of age. Until late stages of dehydration, most infants are alert, active, and hungry despite frequent emesis. Management is almost always surgical after correction of electrolyte abnormalities, and postoperative prognosis is excellent.

Chronic cough in an adolescent with infantile onset of hypokalemic hypochloremic metabolic alkalosis: Questions.

Chronic cough in an adolescent with infantile onset of hypokalemic hypochloremic metabolic alkalosis: Questions.

Chronic cough in an adolescent with infantile onset of hypokalemic hypochloremic metabolic alkalosis: Answers.

Chronic cough in an adolescent with infantile onset of hypokalemic hypochloremic metabolic alkalosis: Answers.