Hypokalemic Metabolic Alkalosis Research Articles

Hypokalemic metabolic alkalosis in an adolescent female: Questions.

Hypokalemic metabolic alkalosis in an adolescent female: Questions.

Hypokalemic metabolic alkalosis in an adolescent female: Answers.

Hypokalemic metabolic alkalosis in an adolescent female: Answers.

Gitelman syndrome and ectopic calcification in the retina and joints.

Gitelman syndrome is a rare inherited renal tubular disorder with features that resemble thiazide use, including a hypokalemic metabolic alkalosis, hypomagnesemia, hypocalciuria and a low or normal blood pressure, hyperreninemia and hyperaldosteronism. Treatment is primarily correction of the potassium and magnesium levels. The diagnosis is confirmed with genetic testing but Gitelman syndrome is often not suspected. However, the association with ectopic calcification in the retina, blood vessels and chondrocalcinosis in the joints is a useful pointer to this diagnosis. Bilateral symmetrical whitish deposits of calcium pyrophosphate are visible superotemporally on ophthalmoscopy and retinal photography but are actually located beneath the retina in the sclerochoroid. Optical coherence tomography is even more sensitive for their detection. These deposits increase in size with time, but the rate of progression slows with long-term correction of the hypomagnesemia. Calcification may be complicated by atrophy of the overlying retina and visual loss. The deposits often correlate with ectopic calcification in the aorta and coronary and cerebral vessels. Chondrocalcinosis occurs in the large joints such as the knees. Ectopic calcification in Gitelman syndrome indicates the need for more aggressive management of Mg levels. Calcification is much less common in Bartter syndrome, which itself is rarer and associated less often with hypomagnesemia.

Pseudo-Bartter syndrome presenting a preschooler with cystic fibrosis

Children with cystic fibrosis (CF) are at increased risk of developing electrolyte abnormalities. In cases of extreme electrolyte and fluid losses (e.g., vomiting and diarrhea) they may present pseudo-Bartter syndrome (PBS)1 characterized by hypokalemic and hypochloremic metabolic alkalosis in the absence of renal tubular disease2. In this condition, the renin-angiotensin-aldosterone is activated, in response to extracellular volume depletion and hyponatremia. PBS most commonly presents in infants under 6 months old. However, an association with high ambient temperatures and seasonal epidemics has been reported in countries with warm weather3, when losses of chlorine and sodium in sweat are increased. There is no data on the incidence of PBS as a complication of CF in Latin America. Retrospective case series studies from Jordan, Turkey and Saudi Arabia suggested an incidence range of 12-18.3% in their pediatric populations2,4,5.

SÍNDROME DE BARTTER NO DIAGNÓSTICO DIFERENCIAL DE BAIXA ESTATURA: UM RELATO DE CASO

This article aims to present a case report involving Bartter syndrome in the differential diagnosis of short stature. This is a retrospective study, based on a prospective, descriptive, observational protocol of the case report type. The report involved a term newborn, without complications, vigorous, weighing 3.560g, measuring 50cm with gestational history of polyhydramnios at 27 weeks, initially attributed to gestational diabetes. When approaching patients under investigation for short stature, the relevance of suspicion of this etiology by the generalist pediatrician in the differential diagnosis is reiterated, since through the early inclusion of venous gasometry and ionogram in laboratory tests the result is almost pathognomonic, low cost, widely accessible, and capable of dispensing with onerous and superfluous research. In conclusion, Bartter syndrome is a rare tubulopathy that often has weight and neuropsychomotor deficit, whose early therapy allows long-term complications to be attenuated. Diagnostic strongly suggested by gasometry, typically presenting hypokalemic metabolic alkalosis. Due to the widely accessible propaedeutic, its investigation is imperative in the patient with short stature.

Impaired Distal Tubular Acidification, Renal Cysts and Nephrocalcinosis in Monogenic Hypertension.

Monogenic defects in tubular sodium handling contribute a small proportion to hypertension in childhood. Presentation varies from severe hypertension manifesting at birth to asymptomatic hypertension and hypokalemic metabolic alkalosis detected incidentally in adulthood. A 12-y-old girl presenting with polyuria, polydipsia, severe hypertension and seizures, was found to have hypokalemia, renal medullary cysts and nephrocalcinosis. Clinical exome revealed a homozygous variation of unknown significance in exon 5 of the HSD11B2 gene, indicating the diagnosis of apparent mineralocorticoid excess. Therapy with spironolactone was associated with resolution of hypokalemia and normal blood pressure during two-year follow up.

Bartter Syndrome in Children; A Cause of Severe Hypokalemic Metabolic Alkalosis: Clinical Case Report and Literature Review

Bartter syndrome is an inherited renal tubular disorder caused by a defective salt reabsorption in the thick ascending limb of loop of Henle. It characterized by urinary loss of sodium, potassium, and chloride; hypokalemic metabolic alkalosis; normal blood pressure, high plasma levels of renin and aldosterone. There is phenotypical and genetic variability of Bartter syndrome since were identified five genes responsible for five different forms of Bartter syndrome. The objective of this work is to report a clinical case to study the pathophysiological, clinical, biological and therapeutic features of this syndrome.
 Materials and Methods: We reported a case of 04-month-old male infant admitted for acute dehydration secondary to polyuro-polydipsia syndrome and vomiting. In clinical presentation the patient had a dysmorphic syndrome with triangular face, protruding ears and flattened nasal root. Laboratory tests revealed hypokalemia, hyponatremia, metabolic alkalosis and hypercalciuria. Treatment with indomethacin was started at 1 mg/kg per day with favorable outcome.

Transient hyponatremia of prematurity caused by mild Bartter syndrome type II: a case report

BackgroundBartter syndrome subtypes are a group of rare renal tubular diseases characterized by impaired salt reabsorption in the tubule, specifically the thick ascending limb of Henle’s loop. Clinically, they are characterized by the association of hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, increased levels of plasma renin and aldosterone, low blood pressure and vascular resistance to angiotensin II. Bartter syndrome type II is caused by mutations in the renal outer medullary potassium channel (ROMK) gene (KCNJ1), can present in the newborn period and typically requires lifelong therapy.Case presentationWe describe a case of a prematurely born female infant presenting with antenatal polyhydramnios, and postnatal dehydration and hyponatremia. After 7 weeks of sodium supplementation, the patient demonstrated complete resolution of her hyponatremia and developed only transient metabolic alkalosis at 2 months of age but continues to be polyuric and exhibits hypercalciuria, without development of nephrocalcinosis. She was found to have two pathogenic variants in the KCNJ1 gene: a frameshift deletion, p.Glu334Glyfs*35 and a missense variant, p. Pro110Leu. While many features of classic ROMK mutations have resolved, the child does have Bartter syndrome type II and needs prolonged pediatric nephrology follow-up.ConclusionTransient neonatal hyponatremia warrants a multi-system workup and genetic variants of KCNJ1 should be considered.

A 5-year-old boy with refractory rickets, polyuria, and hypokalemic metabolic alkalosis: Questions.

A 5-year-old boy with refractory rickets, polyuria, and hypokalemic metabolic alkalosis: Questions.

A 5-year-old boy with refractory rickets, polyuria, and hypokalemic metabolic alkalosis: Answers.

A 5-year-old boy with refractory rickets, polyuria, and hypokalemic metabolic alkalosis: Answers.

Research process in molecular genetics of Gitelman syndrome

Gitelman syndrome(GS) is an autosomal recessive genetic disease caused by mutations in the SLC12A3 gene located in chromosome 16q13. The incidence of GS is 1-10∶40 000. SLC12A3 encodes thiazide-sensitive sodium-chloride cotransporters(NCC) which play key roles in Na+ and Cl- reabsorption. GS is characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesaemia and low urinary calcium excretion. There are some correlations between genotypes and phenotypes. In previous studies, more than 500 mutations have been identified and some of them have been functionally analyzed. We review genetic mutations and functional studies related to GS as well as the relationship between genotypes and phenotypes, and summarize the research process in molecular genetics of GS. Key words: Gitelman syndrome; Na+ /Cl- cotransporter; SLC12A3 gene mutation

A rare case of severe hypertension with hypokalemic metabolic alkalosis in a 14-year-old girl: Answers.

A rare case of severe hypertension with hypokalemic metabolic alkalosis in a 14-year-old girl: Answers.

A rare cause of severe hypertension with hypokalemic metabolic alkalosis in a 14-year-old girl: Questions.

A rare cause of severe hypertension with hypokalemic metabolic alkalosis in a 14-year-old girl: Questions.

Splicing Characterization of CLCNKB Variants in Four Patients With Type III Bartter Syndrome.

ObjectiveType III Bartter syndrome (BS) is caused by loss-of-function mutations in the gene encoding basolateral chloride channel ClC-Kb (CLCNKB), and is characterized by hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism. Here, we investigated the molecular defects in four Chinese children with clinical manifestations of Bartter syndrome.MethodsThe genomic DNA of the four patients was screened for gene variations using whole-exome sequencing (WES). The candidate variants were validated by direct Sanger sequencing. Quantitative PCR (qPCR) was subsequently performed to confirm the whole CLCNK gene deletion mutation. A minigene assay and reverse transcription PCR (RT-PCR) were performed to analyze the effect of splice variants in vitro.ResultsOur patients showed early onset age with hyponatremia, hypokalemia, hypochloremia, repeated vomiting and growth retardation, suggesting Bartter syndrome. Genetic analysis revealed that all patients carried compound heterozygous or homozygous truncating variants in the CLCNKB gene. In particular, we identified a novel nonsense variant c.239G > A (p.(Trp80*)), two splice site variants (c.1053-1 G > A and c.1228-2A > G), a whole gene deletion, and a novel synonymous variant c.228A > C (p.(Arg76Arg)) which located -2 bp from the 5′ splice donor site in exon 3. Furthermore, our in vitro minigene analysis revealed c.228A > C, c.1053-1G > A, and c.1228-2A > G cause the skipping of exon 3, exon 12, and exon 13, respectively.ConclusionOur results support that the whole CLCNKB gene deletion is the most common mutation in Chinese patients with type III BS, and truncating and whole gene deletion variants may account for a more severe phenotype of patients. We verified the pathogenic effect of three splicing variants (c.228A > C, c.1053-1G > A, and c.1228-2A > G) which disturbed the normal mRNA splicing, suggesting that splice variants play an important role in the molecular basis of type III BS, and careful molecular profiling of these patients will be essential for future effective personalized treatment options.

An unusual cause for hypokalemic metabolic alkalosis with medullary nephrocalcinosis

Bartter syndrome is a rare inherited tubulopathy characterized by hypokalemic metabolic alkalosis, polyuria, growth retardation, and often, medullary nephrocalcinosis. Many disorders present with similar clinical and metabolic features and pose diagnostic dilemma. We describe a young infant girl with growth retardation, hypokalemic metabolic alkalosis, and medullary nephrocalcinosis but without polyuria or urinary chloride wasting. Clinical exome sequencing revealed compound heterozygous variations in SLC26A3 (c.1514+5G > A and c.168del), the gene implicated in congenital chloride diarrhea. This case highlights the utility of genetic testing for definitive diagnosis and specific management in cases where Bartter syndrome is suspected.

Classical bartter's syndrome (Type III) with deafness: A very rare case management

Bartter syndrome (BS) represents a group of autosomal recessive salt-losing nephropathy, characterized by hypokalemic metabolic alkalosis with normal or low blood pressure. Hearing defect is a feature of BS Type IV and is typically absent in BS I, II, or III. We report the case of a 2-year-old boy with severe to profound sensory neural deafness who diagnosed with BS Type III in the neonatal period. His deafness was noted at 9 months. He used hearing aids regularly for 1 year with very limited benefit, an aided visual reinforcement audiometry test resulted in a reading of only 55 dB. Cochlear implantation was performed at the age of 3 years with excellent postoperative audiometric results and improvement in speech performance. To the best of our knowledge, this is the second-documented case of BS Type III with bilateral sensory neural deafness and the first-reported case of cochlear implantation in such a patient.

Electrolytes, Serum biochemical and Acid-Base Disturbances in Dogs with Foul-Smelling Bloody Diarrhoea

Metabolic alkalosis is an electrolyte abnormality accompanied by an elevation in bicarbonate ion concentration in blood and a rise in blood pH. This study aims to determine the serum concentration of electrolytes and levels of some biochemical parameters in dogs presented with profuse foul-smelling bloody watery diarrhoea. From October 2018 to February 2019, 60 client-owned dogs were presented at the University of Nigeria Veterinary Teaching Hospital (UNVTH) for vaccination, treatment and regular deworming. Five (5) out of 60 dogs had profuse foul-smelling watery diarrhoea and were sampled. A full history and physical examinations were undertaken for the sampled dogs. Clinical signs such as profuse foul-smelling bloody diarrhoea, vomiting, anorexia, weakness, dehydration, lethargy was observed in the affected dogs. Three dogs were 4 months old while two dogs are adults. Blood samples (2 ml) were collected from the cephalic vein of dogs with the above presentation, and sera were harvested for serum biochemical analysis. Standard procedures were followed in all the serum biochemistry determinations. The most common electrolyte and serum biochemical abnormalities in 5 dogs with profuse foul-smelling bloody watery diarrhoea were hypokalemia (100%), increased serum bicarbonate level (100%), hyponatremia (75%), and hypoglobulinemia (100%). Hypochloremia occurred in 20% of the cases, while hypoproteinemia, hypoglobulinemia, and low serum creatinine levels were recorded in 100% of the cases. Increased urea level was observed in 40% of the affected dogs. Our study demonstrated that all affected dogs developed hypokalemic metabolic alkalosis following loss of potassium through the gastrointestinal tract consequent upon severe watery diarrhoea.

Gitelman Syndrome: What the Clinician Needs to know

Gitelman syndrome has a prevalence of 1-10/40.000, representing the most common inherited disease of renal tubules. It is due to inactivating mutations of the SLC12A3 gene that encodes the thiazide-sensitive Sodium Chloride Cotransporter (NCC) located in the apical membrane of the distal convoluted tubules, resulting in hypokalemic metabolic alkalosis associated with hypomagnesemia and hypocalciuria. Although it is generally considered a benign tubular disease, a number of complications have been observed in some patients.

Adjunctive acetazolamide therapy for the treatment of Bartter syndrome.

Bartter syndrome is a rare hereditary salt-losing tubulopathy caused by mutations of several genes in the thick ascending limb of Henle's loop, characterized by polyuria, hypokalemic metabolic alkalosis, growth retardation and normal blood pressure. Cyclooxygenase inhibitors, potassium-sparing diuretics and angiotensin-converting enzyme inhibitors are currently used to treat electrolyte derangements, but with poor response. Whether treatment with acetazolamide, a carbonic-anhydrase inhibitor, would result in better clinical outcomes is unknown. We randomly assigned children with Bartter syndrome in a 1:1 ratio to either receive indomethacin, enalapril, and spironolactone or indomethacin, enalapril, and spironolactone plus acetazolamide once daily in the morning for 4weeks. After 2days of washout, participants crossed over to receive the alternative intervention for 4weeks. The present study examines the serum bicarbonate lowering effect of acetazolamide as an adjunctive therapy in children with Batter syndrome. Of the 43 patients screened for eligibility, 22 (51%), between the ages 6 and 42months, were randomized to intervention. Baseline characteristics were similar between the two groups. Addition of acetazolamide for a period of 4weeks significantly reduced serum bicarbonate and increased serum potassium levels, parallel with a reduction in serum aldosterone and plasma renin concentration. The 24-h urine volume, sodium, potassium, and chloride decreased significantly. Our data define a new physiologic and therapeutic role of acetazolamide for the management of children with Bartter syndrome.

Hypokalemia and hearing loss in a 3-year-old boy: Questions.

Bartter syndrome with sensorineural deafness (Bartter syndrome type 4) is an autosomal recessive disorder characterized with polyhydramniosis, premature birth, massive polyuria, renal salt-wasting, hypokalemic metabolic alkalosis, normotensive hyperreninemic hyperaldosteronism, and hearing loss. Homozygous mutations in BSND, CLCNKA, and CLCNKB mutations cause the disorder. Here we report a 3-year-old boy who had not been evaluated and investigated before cochlear implantation. Hypokalemia was detected during the routine laboratory workup before surgery. Further analyses revealed metabolic alkalosis with high renin and aldosterone levels. Hypokalemia improved with oral potassium chloride supplementation. Genetic tests revealed a homozygous c.139G>A (pG47R) mutation in BSND gene, and both parents were heterozygous for the same mutation. We want to emphasize the importance of evaluating hearing loss in children, since some of the genetic syndromes may cause life threatening abnormalities.