A case of pseudo-Bartter/Gitelman syndrome caused by long-term laxative abuse, leading to end-stage kidney disease.

Pseudo-Bartter/Gitelman syndrome (PBS/PGS) is a disorder that presents with hypokalemia and metabolic alkalosis resembling Gitelman syndrome (GS) due to secondary factors, such as lifestyle and /or medicines. Notably, PBS/PGS is more likely to cause renal dysfunction than GS. We report the first case of PBS/PGS due to long-term laxative abuse leading to end-stage kidney disease (ESKD). The patient was a 49-year-old woman with a history of constipation since school, who had used excessive doses of laxatives on her own judgment for nine years at least from 22 years of age. Two years later, blood tests revealed hypokalemia (serum K 3.1 mEq/L), and nine years later, the patient's renal function began to deteriorate (Cr-eGFR 48.7 mL/min/1.73 m2). Since abuse of laxatives was suspected as the cause, it was changed to the proper dosage of laxatives. At 33 years, the patient developed acute kidney injury (AKI), due to a urinary tract infection, and required intensive treatment, including hemodialysis. Although the patient was eventually weaned off dialysis, the renal function did not recover to pre-AKI levels. In suspected GS, comprehensive genetic testing for renal disease-related genes was performed; however, no obvious pathogenic variants were identified. Thereafter, despite decreasing the laxative doses and potassium supplementation, her renal function continued to decline. At 49 years, the patient developed ESKD and was started on maintenance hemodialysis. PBS/PGS is a disease that can lead to ESKD. An early diagnosis of PBS/PGS is crucial to prevent renal function deterioration, and the underlying causes should be removed immediately.

Bartter syndrome-like phenotype in a patient with type 2 diabetes mellitus.

Bartter syndrome (BS) is a rare genetic tubulopathy affecting the loop of Henle leading to salt wasting. It is commonly seen in utero or in the early neonatal period. Rare cases of acquired BS are reported in association with infections like tuberculosis, granulomatous conditions like sarcoidosis, autoimmune diseases and drugs. The mainstay of management includes potassium, calcium and magnesium supplementation. We report the case of a woman in her 50s with a history of type 2 diabetes mellitus for the last 10 years, who presented with diabetic foot ulcers and generalised weakness with ECG changes suggestive of hypokalaemia. She had severe hypokalaemia with high urine potassium excretion and hypochloraemic metabolic alkalosis. She poorly responded to intravenously administered potassium supplements and had persistent hypokalaemia. On further evaluation of the persistent hypokalaemia, a diagnosis of idiopathic Bartter-like phenotype was made. She responded well to tablet indomethacin and is presently asymptomatic and is being maintained on tablet indomethacin after 6 months of follow-up.

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.

Acquired autoimmune Bartter syndrome in a patient with primary hypothyroidism.

We describe an unusual clinical presentation of autoimmune Bartter syndrome in a patient with primary hypothyroidism. A 65-year-old female patient was admitted with neuromuscular weakness associated with hypokalemia and metabolic alkalosis. She had a suboptimal response to potassium supplementation and potassium-sparing diuretic resulting in re-hospitalization with the same symptoms. A detailed serum and urinary biochemistry analysis in the absence of other causes of potassium wasting helped diagnose Bartter syndrome, a rare entity in adults. An autoimmune profile showed anti-Scl-70 antibody to be positive, although she did not develop other systemic features of the disease. Our patient responded to a steroid-based regimen potassium supplement, Indomethacin, and aldosterone antagonist with remarkable resolution of symptoms and correction of electrolyte derangement. We reviewed the literature to search for similar cases and included twenty-seven full-length publications on acquired and autoimmune causes of Bartter syndrome. Our case highlights the fact that hypokalemia with metabolic alkalosis in an adult patient should prompt clinicians to evaluate for common and uncommon conditions. While assessing for abnormal conditions, acquired Bartter syndrome should be considered if a patient has an underlying autoimmune, endocrine, or connective tissue disease.

Type-5 Bartter syndrome presenting with metabolic seizure in adulthood.

Bartter syndrome is a very rare and heterogeneous disease with variable age of onset and symptom severity. Genotypically they have inherited disorders of the thick ascending limb in the renal tubular system, which manifest phenotypically as electrolyte imbalance due to loss of sodium, chloride and potassium. Gain of function mutations in the calcium-sensing receptor has been described in some patients with Bartter's syndrome (type-5 Bartter syndrome or autosomal dominant hypocalcaemia with Bartter syndrome) associated with hypocalcaemia and hypercalciuria differentiating it from Gitelman syndrome. This phenotype has been reported to present in adulthood with metabolic abnormalities. We present a case of a middle-aged woman who presented with metabolic seizures and on evaluation was found to have profound electrolyte abnormalities which were corrected with supplements and led to the resolution of symptoms.

Pseudo-Bartter syndrome in Chinese children with cystic fibrosis: Clinical features and genotypic findings.

OBJECTIVES: To characterize the clinical and genotypic features of cystic fibrosis-associated pseudo-Bartter syndrome (CF-PBS) in Chinese children. METHODS: We recruited and characterized the clinical manifestations of 12 Chinese children with CF-PBS. Sweat test, blood and urinary analysis, sputum culture, chest and sinus computed tomography, and abdominal ultrasonography were obtained. Whole-exome sequencing, bioinformatics analysis, and Sanger sequencing validation were performed to define the genotypes. RESULTS: CF-PBS was accompanied by recurrent and/or persistent pneumonia (91.7%), pancreatitis (83.3%), vomiting and/or diarrhea (66.7%), failure to thrive and liver disease (58.3% respectively), among our patients. The predominant organisms found in the airways were Pseudomonas aeruginosa (83.3%) and Staphylococcus aureus (75.0%). The mean concentrations of blood gas and electrolytes were pH 7.58, bicarbonate 40.8 mmol/L, sodium 125.9 mmol/L, chloride 77.5 mmol/L, and potassium 2.6 mmol/L. A high recurrence rate (50.0%) of CF-PBS was observed despite continued electrolyte supplementation during follow-up. In all, 19 different variants of CFTR gene were identified, and 10 of these were found to be novel observations (c.262_266delTTATA[p.L88FfsX21], c.579+2insACAT, c.1210-3C>G, c.1733T>C[p.L578P], c.2236_2246delGAGGCGATACTinsAAAAATC[p.E746KfsX8], c.3068T>G [p.I1023R], c.3635delT[p.V1212AfsX16], c.3859delG[p.G1287EfsX2], c.3964-7A>G and ΔE23 [c.3718-?_3873+?del]). The c.2909G>A[p.G970D] was the most common variant, with an allele frequency of 16.6%. A homozygous genotype of c.1521_1523delCTT[p.F508del] was discovered for the first time in patients of Chinese origin. CONCLUSIONS: In China, CF-PBS usually presents early and recurs frequently in infancy, accompanied by multiple comorbidities. Recurrence of CF-PBS in school-going patients does occur but is rare. The p.G970D is the most frequent variant, with a significant ethnic tendency of Chinese origin.

[Bartter-Gitelman syndromes]. / Syndromes de Bartter­Gitelman.

Bartter-Gitelman syndromes are rare inherited autosomal recessive salt-losing tubulopathies characterized by severe and chronic hypokalemia associated with metabolic alkalosis and secondary hyperaldosteronism. Bartter syndrome results from a furosemide-like defect in sodium reabsorption in the Henle's loop leading to hypercalciuria and defect in urinary concentration capacity. The antenatal Bartter syndrome is defined by polyhydramnios and an infantile polyuria with severe dehydration whereas classic Bartter syndrome appears during childhood or adulthood. Gitelman syndrome is a thiazide-like salt-losing tubulopathy. It is associated with hypomagnesemia, hypocalciuria without defect in urinary concentration capacity. The diagnosis is most often made in adolescents or adults. Clinical symptoms include tetany, delay in the height-weight growth curves, chronic tiredness, muscle weakness, myalgia and vertigo. Nephrocalcinosis in Bartter syndrome could lead to chronic kidney disease. Antenatal Bartter syndrome requires hospitalization in intensive care unit to manage the severe newborn dehydration. Chondrocalcinosis is the major complication in the Gitelman syndrome. The corner stones of treatment is the fluid and electrolyte management Bartter and Gitelman syndromes need lifelong oral supplementations of potassium, salt (Bartter) and magnesium (Gitelman). Indomethacin is efficient to reduce water and electrolyte loss in Bartter. In Gitelman, potassium-sparing diuretics may be helping for severe hypokaliemia but they will reinforce hypovolemia.

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

BACKGROUND: Bartter 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 PRESENTATION: We 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. CONCLUSION: Transient neonatal hyponatremia warrants a multi-system workup and genetic variants of KCNJ1 should be considered.

A novel compound heterozygous KCNJ1 gene mutation presenting as late-onset Bartter syndrome: Case report.

RATIONALE: Bartter syndrome is an autosomal-recessive inherited disease in which patients present with hypokalemia and metabolic alkalosis. We present 1 case with Bartter syndrome, due to a novel compound heterozygous mutation in the KCNJ1 gene encoding the ATP-sensitive inward rectifier potassium channel in the thick ascending limb of the loop of Henle. PATIENT CONCERNS: A patient was admitted to our hospital because of weakness, polyuria, and polydipsia. At presentation to our hospital, the female Chinese patient was 34 years old and her physical examination was normal. Laboratory studies revealed hypokalemia, metabolic alkalosis, hypercalciuria, hyperparathyroidemia, and hyper-reninemia. In addition, urinary potassium was obviously higher. Computer tomography scan confirmed the patient had the bilateral medullary nephrocalcinosis. DIAGNOSIS: Blood samples were received from the patient and her parents, and deoxyribonucleic acid was extracted. The genetic analysis of SLC12A1, SLC12A3, KCNJ1, CLCNKB, BSND, and CASR was performed. The compound heterozygous KCNJ1 gene mutation was validated using conventional Sanger sequencing methods. INTERVENTIONS: The patient was treated with potassium supplementation. Her blood and urine chemistries improved over the next week. Serum potassium normalized with improvement in polyuria and polydipsia over the next month. OUTCOMES: Our patient was compound heterozygous for Thr234Ile and Thr71Met in the KCNJ1 gene. The c.701C>T variant predicted a change from a threonine codon to an isoleucine codon (p.Thr234Ile). The c.212C>T variant predicted a change from a threonine codon to a methionine codon (p.Thr71Met). The unaffected mother was heterozygous for the Thr234Ile mutation, whereas unaffected father was heterozygous for the Thr71Met mutation. LESSONS: The phenotypes of the patient were similar to other patients with Bartter syndrome. The phenotypes of the patient could eventually be explained by the presence of the novel compound heterozygous p.Thr234Ile/p.Thr71Met variants in the KCNJ1 gene.

Bartter syndrome-like phenotype in a patient with diabetes: a case report.

BACKGROUND: Bartter's syndrome is a rare genetic tubulopathy affecting the loop of Henle leading to salt wasting. It is commonly seen in utero or in early neonatal period. Rare cases of acquired Bartter's syndrome are reported in association with infections like tuberculosis, granulomatous conditions like sarcoidosis, autoimmune diseases, and drugs. The mainstay of management includes potassium, calcium, and magnesium supplementation. CASE PRESENTATION: We report the case of a 62-year-old Sri Lankan Sinhalese man with diabetes and hypertension presenting with generalized weakness with clinical evidence of proximal myopathy. He was severely hypokalemic with high urinary potassium excretion and hypochloremic metabolic alkalosis. He poorly responded to intravenously administered potassium supplements. A diagnosis of idiopathic Bartter-like phenotype was made. He responded well to spironolactone and indomethacin. CONCLUSIONS: Patients presenting with body weakness need serum potassium estimation. Acquired Bartter's syndrome although rare, should be ruled out in those with hypokalemia and metabolic alkalosis with increased urinary potassium loss with poor response to potassium replacement.

Identification of the Causes for Chronic Hypokalemia: Importance of Urinary Sodium and Chloride Excretion.

BACKGROUND: Uncovering the correct diagnosis of chronic hypokalemia with potassium (K+) wasting from the kidneys or gut can be fraught with challenges. We identified clinical and laboratory parameters helpful for differentiating the causes of chronic hypokalemia. METHODS: Normotensive patients referred to our tertiary academic medical center for the evaluation of chronic hypokalemia were prospectively enrolled over 5 years. Clinical features, laboratory examinations-including blood and spot urine electrolytes, acid-base status, biochemistries, and hormones-as well as genetic analysis, were determined. RESULTS: Ninety-nine patients with chronic normotensive hypokalemia (serum K+ 2.8 ± 0.4 mmol/L, duration 4.1 ± 0.9 years) were enrolled. Neuromuscular symptoms were the most common complaints. Although Gitelman syndrome (n = 33), Bartter syndrome (n = 10), and distal renal tubular acidosis (n = 12) were the predominant renal tubular disorders, 44 patients (44%) were diagnosed with anorexia/bulimia nervosa (n = 21), surreptitious use of laxatives (n = 11), or diuretics (n = 12). Patients with gastrointestinal causes and surreptitious diuretics use exhibited a female predominance, lower body mass index, and less K+ supplementation. High urine K+ excretion (transtubular potassium gradient >3, urine K+/Cr >2 mmol/mmol) was universally present in patients with renal tubular disorders, but also found in >50% patients with gastrointestinal causes. Of interest, while urine sodium (Na+) and chloride (Cl-) excretions were high and coupled (urine Na+/Cl- ratio ∼1) in renal tubular disorders and "on" diuretics use, skewed or uncoupled urine Na+ and Cl- excretions were found in anorexia/bulimia nervosa and laxatives abuse (urine Na+/Cl- ratio: 5.0 ± 2.2, 0.4 ± 0.2, respectively) and low urine Na+ and Cl- excretions with fixed Na+/Cl- ratios (0.9 ± 0.2) when "off" diuretics. CONCLUSION: Besides body mass index, sex, and blood acid-base status, integrated interpretation of the urine Na+:Cl- excretion and their ratio is important to make an accurate diagnosis and treatment plan for patients with chronic normotensive hypokalemia.

Accentuated hyperparathyroidism in type II Bartter syndrome.

BACKGROUND: Bartter syndrome (BS) may be associated with different degrees of hypercalciuria, but marked parathyroid hormone (PTH) abnormalities have not been described. METHODS: We compared clinical and laboratory data of patients with either ROMK-deficient type II BS (n = 14) or Barttin-deficient type IV BS (n = 20). RESULTS: Only BS-IV patients remained mildly hypokalemic in spite of a higher need for potassium supplementation. Estimated glomerular filtration rate (eGFR) was mildly decreased in only four BS-IV patients. Average PTH values were significantly higher in BS-II (160.6 ± 85.8 vs. 92.5 ± 48 pg/ml in BS-IV, p = 0.006). In both groups, there was a positive correlation between age and log(PTH). Levels of 25(OH) vitamin D were not different. Total serum calcium was lower (within normal limits) and age-related serum phosphate (Pi)-SDS was increased in BS-II (1.19 ± 0.71 vs. 0.01 ± 1.04 in BS-IV, p < 0.001). The GFR threshold for Pi reabsorption was higher in BS-II (5.63 ± 1.25 vs. 4.36 ± 0.98, p = 0.002). Spot urine calcium/creatinine ratio and nephrocalcinosis rate (100 vs. 16 %) were higher in the BS-II group. CONCLUSIONS: PTH, serum Pi levels, and urinary threshold for Pi reabsorption are significantly elevated in type II vs. type IV BS, suggesting a PTH resistance state. This may be a response to more severe long-standing hypercalciuria, leading to a higher rate of nephrocalcinosis in BS-II.

Diagnóstico casual de un síndrome de Gitelman / Casual diagnosis of Gitelman's syndrome

El síndrome de Gitelman es una tubulopatía de herencia autosómica recesiva en el que la alteración fundamental se halla en el túbulo distal, concretamente a nivel del cotransportador Na/Cl, sensible a las tiazidas, codificado en el cromosoma 16q. Cursa con alcalosis metabólica con normotensión, hipopotasemia, así como hipomagnesemia e hipocalciuria que la diferencian del síndrome de Bartter. Su diagnóstico puede demorarse hasta la edad adulta ya que los pacientes pueden mantenerse asintomáticos durante largos períodos de tiempo. El tratamiento consiste en suplementos orales de potasio y magnesio, así como también se ha descrito la utilidad de diuréticos ahorradores de potasio e indometacina (AU)

Gitelman's syndrome is a renal tubule disease of recessive autosomal inheritance in which the fundamental alteration is found in the distal tubule, specifically at the level of the Na/Cl cotransporter, is sensitive to thiazides, and coded in chromosome 16q. It is characterised by a metabolic alkalosis with normal blood pressure, hypokalaemia, as well as hypomagnesaemia and hypocalciuria, which separate it from Bartter's syndrome. Its diagnosis can be delayed up to the adult age, as patients may remain asymptomatic for long periods of time. The treatment consists of oral supplements of potassium and magnesium, and the use of potassium-sparing diuretics and indomethacin has also been described (AU)

Treatment of Bartter syndrome. Unsolved issue, / Tratamento da síndrome de Bartter. Problema não resolvido,

Objective: To describe the results of a long-term follow-up of Bartter syndrome patients treated with different drugs. Method: Patients were diagnosed according to clinical and laboratory data. Treatment protocol was potassium supplementation, sodium, spironolactone, and non-steroidal anti-inflammatory drug. Patients who developed proteinuria were converted to angiotensin conversion enzyme inhibitor. The variables evaluated for each drug were Z-score for weight and stature, proteinuria, creatinine clearance, gastrointestinal complaints, amount of potassium supplementation, serum potassium and bicarbonate levels, and findings of upper digestive endoscopy. Results: 20 patients were included. Follow-up was 10.1 ± 5.2 years. 17 patients received indomethacin for 5.9 ± 5.3 years; 19 received celecoxib, median of 35 months; and five received enalapril, median of 23 months. During indomethacin, a statistically significant increase was observed in the Z-score for stature and weight, without a change in the creatinine clearance. Seven of 17 patients had gastrointestinal symptoms, and upper digestive endoscopy evidenced gastritis in three patients and gastric ulcer in four patients. During celecoxib use, a significant increase was detected in the Z-score for stature and weight and a reduction of hyperfiltration; seven patients presented gastrointestinal symptoms, and upper digestive endoscopy evidenced mild gastritis in three. During enalapril use, no significant changes were observed in the Z-score for stature, weight and creatinine clearance. The conversion to enalapril resulted in a significant reduction in proteinuria. Conclusion: The authors suggest starting the treatment with celecoxib, and replacing by ACEi if necessary, monitoring the renal function. The safety and efficacy of celecoxib need to be assessed in larger controlled studies. .

Objetivo: Descrever os resultados de um acompanhamento de longo prazo de pacientes com síndrome de Bartter tratados com diferentes medicamentos. Método: Pacientes diagnosticados segundo os dados clínicos e laboratoriais. Protocolo de tratamento: suplementação de potássio, sódio, espironolactona e medicamento anti-inflamatório não esteroidal. Os pacientes que desenvolveram proteinúria foram submetidos a inibidor da enzima de conversão da angiotensina. As variáveis avaliadas durante o uso de cada medicamento foram: escore Z para peso e estatura, proteinúria, depuração da creatinina, queixas gastrointestinais, quantidade da suplementação de potássio, níveis séricos de potássio e bicarbonato e achados da endoscopia digestiva alta. Resultados: Foram incluídos 20 pacientes. O acompanhamento foi de 10,1 ± 5,2 anos. No total, 17 pacientes receberam indometacina por 5,9 ± 5,3 anos, 19 receberam celecoxib por aproximadamente 35 meses e cinco receberam enalapril por aproximadamente 23 meses. Durante o uso de indometacina, observamos um aumento estatístico significativo no escore Z para estatura e peso, sem alteração na depuração da creatinina. 7/17 pacientes apresentaram sintomas gastrointestinais, e a endoscopia digestiva alta mostrou gastrite em três pacientes e úlcera gástrica em quatro. Durante o uso de celecoxib, detectamos um aumento significativo no escore Z para estatura e peso e uma redução da hiperfiltração; sete pacientes apresentaram sintomas gastrointestinais e a endoscopia digestiva alta mostrou gastrite leve em três pacientes. Durante o uso de enalapril, não observamos alterações significativas no escore Z para estatura, peso e depuração da creatinina. A mudança da medicação para enalapril resultou em uma ...

Treatment of Bartter syndrome. Unsolved issue.

OBJECTIVE: To describe the results of a long-term follow-up of Bartter syndrome patients treated with different drugs. METHOD: Patients were diagnosed according to clinical and laboratory data. Treatment protocol was potassium supplementation, sodium, spironolactone, and non-steroidal anti-inflammatory drug. Patients who developed proteinuria were converted to angiotensin conversion enzyme inhibitor. The variables evaluated for each drug were Z-score for weight and stature, proteinuria, creatinine clearance, gastrointestinal complaints, amount of potassium supplementation, serum potassium and bicarbonate levels, and findings of upper digestive endoscopy. RESULTS: 20 patients were included. Follow-up was 10.1 ± 5.2 years. 17 patients received indomethacin for 5.9 ± 5.3 years; 19 received celecoxib, median of 35 months; and five received enalapril, median of 23 months. During indomethacin, a statistically significant increase was observed in the Z-score for stature and weight, without a change in the creatinine clearance. Seven of 17 patients had gastrointestinal symptoms, and upper digestive endoscopy evidenced gastritis in three patients and gastric ulcer in four patients. During celecoxib use, a significant increase was detected in the Z-score for stature and weight and a reduction of hyperfiltration; seven patients presented gastrointestinal symptoms, and upper digestive endoscopy evidenced mild gastritis in three. During enalapril use, no significant changes were observed in the Z-score for stature, weight and creatinine clearance. The conversion to enalapril resulted in a significant reduction in proteinuria. CONCLUSION: The authors suggest starting the treatment with celecoxib, and replacing by ACEi if necessary, monitoring the renal function. The safety and efficacy of celecoxib need to be assessed in larger controlled studies.

Hypokalemic paralysis in a middle-aged female with classic Bartter syndrome.

Inherited classic Bartter syndrome (cBS) is an autosomal recessive renal tubular disorder resulting from inactivating mutations in the asolateral chloride channel (C1C-Kb) and usually presents in early infancy or childhood with mild to moderate hypokalemia. Profound hypokalemic paralysis in patients with cBS is extremely rare, especially in middle age. A 45-year-old Chinese female patient was referred for evaluation of chronic severe hypokalemia despite regular K+ supplementation (1 mmol/kg/d). She had had two episodes of muscle paralysis due to severe hypokalemia (K+ 1.9 - 2.1 mmol/l) in the past 3 years. She denied vomiting, diarrhea, or the use of laxatives or diuretics. Her blood pressure was normal. Biochemical studies showed hypokalemia (K+ 2.5 mmol/l) with renal potassium wasting, metabolic alkalosis (HCO3- 32 mmol/l), normomagnesemia (Mg2+ 0.8 mmol/l), hypercalciuria (calcium to creatinine ratio 0.5 mmol/mmol; normal < 0.22 mmol/mol), high plasma renin activity, but normal plasma aldosterone concentration. Abdominal sonography revealed neither renal stones nor nephrocalcinosis. Acquired causes of cBS such as autoimmune disease and drugs were all excluded. Molecular analysis of the CLCNKB gene, encoding ClC-Kb, and SLC12A3, encoding the thiazide-sensitive sodium chloride cotransporter (NCC), revealed compound heterozygous mutations in CLCNKB (L335P and G470E) inherited from her parents; her SLC12A3 was normal. These two mutations were not identified in 100 healthy subjects. Her plasma K+ concentration rose to 3 - 3.5 mmol/l after the addition of spironolactone. Inherited cBS may present with hypokalemic paralysis and should be considered in adult patients with hypokalemia and metabolic alkalosis.

Classic Bartter syndrome: a rare cause of failure to thrive in a child.

Bartter syndrome is a group of rare autosomal-recessive disorders caused by a defect in distal tubule transport of sodium and chloride. Blood gases and plasma electrolytes raise suspicion of this diagnosis and the definitive diagnosis is made by genetic study. Early treatment improves prognosis. The authors present the case of an 11-month-old child with early failure to thrive and severe regurgitation. Blood gases revealed hypochloraemic metabolic alkalosis, hyponatraemia and hypokalaemia. Blood pressure was normal and polyuria was documented. She began therapy with potassium chloride supplementation and indomethacin. There was clinical improvement and plasma potassium and bicarbonate normalised. The molecular study confirmed it was the classic form of Bartter syndrome. Despite being rare in clinical practice, which may lead to unnecessary medical investigation and diagnosis delay, in a child with failure to thrive, hypochloraemic metabolic alkalosis and hypokalaemia, this diagnosis must be considered.

Pseudo-Bartter syndrome in an infant with congenital chloride diarrhoea.

INTRODUCTION: Pseudo-Bartter syndrome encompasses a heterogenous group of disorders similar to Bartter syndrome. We are presenting an infant with pseudo-Bartter syndrome caused by congenital chloride diarrhoea. CASE OUTLINE: A male newborn born in the 37th gestational week (GW) to young healthy and non-consanguineous parents. In the 35th GW a polyhydramnios with bowel dilatation was verified by ultrasonography. After birth he manifested several episodes of hyponatremic dehydration with hypochloraemia, hypokalaemia and metabolic alkalosis, so as Bartter syndrome was suspected treatment with indomethacin, spironolactone and additional intake of NaCl was initiated. However, this therapy gave no results, so that at age six months he was rehospitalized under the features of persistent watery diarrhoea, vomiting, dehydration and acute renal failure (serum creatinine 123 micromol/L). The laboratory results showed hyponatraemia (123 mmol/L), hypokalaemia (3.1 mmol/L), severe hypochloraemia (43 mmol/L), alcalosis (blood pH 7.64, bicarbonate 50.6 mmol/L), high plasma renin (20.6 ng/ml) and aldosterone (232.9 ng/ml), but a low urinary chloride concentration (2.1 mmol/L). Based on these findings, as well as the stool chloride concentration of 110 mmol/L, the patient was diagnosed congenital chloride diarrhoea. In further course, the patient was treated by intensive fluid, sodium and potassium supplementation which resulted in the normalization of serum electrolytes, renal function, as well as his mental and physical development during 10 months of follow-up. CONCLUSION: Persistent watery diarrhoea with a high concentration of chloride in stool is the key finding in the differentiation of congenital chloride diarrhoea from Bartter syndrome. The treatment of congenital chloride diarrhoea consists primarily of adequate water and electrolytes replacement.

Bartter's syndrome in pregnancy: review of potassium homeostasis in gestation.

A 26-year-old G3P2 Hispanic female presented with acute urinary retention and profound hypokalemia (serum potassium 1.6 mEq/L) during her 13th week of pregnancy. Placement of an indwelling bladder catheter resulted in immediate urine output of 1700 mL. Potassium was administered aggressively and urinary retention resolved. She reported the use of herbal products containing licorice and corn silk tea (zea maize extract). She was taking no medication other than prenatal vitamins and had no known prior medical problems. Despite discontinuance of the herbal supplement and tea and aggressive oral potassium replacement, severe asymptomatic hypokalemia persisted. Twenty-four-hour urine studies and blood chemistry determinations, subsequently, were consistent with Bartter's syndrome. At the time of hospital discharge, she was receiving 480 mEq of oral potassium daily. Potassium-sparing diuretics were not prescribed, because successful pregnancy outcomes have been reported in patients with Bartter's syndrome and Gitelman syndrome without normalization of potassium levels. Hypokalemia (2.5-3.0 mEq/L) persisted throughout an otherwise uncomplicated pregnancy with delivery of a healthy child at 35 weeks of gestation.

A case report of an anorexia nervosa patient with end-stage renal disease due to pseudo Bartter's syndrome and Chinese herb nephropathy requiring maintenance hemodialysis.

The extent of end stage renal disease (ESRD) has not been well documented in anorexia nervosa (AN). We herein describe a 47-year-old female with ESRD who required maintenance hemodialysis (HD) following a 27 year history of AN, and seven years of diuretic and purgative abuse. In spite of HD treatment, her serum inorganic phosphorus level remained elevated (10.2-15.8 mg/dL). Tissue degradation due to catabolism, insufficient dialysis treatment, and use of Chinese herbal medicine, including aristolochic acid, are speculated as the cause of her hyperphosphatemia. We also speculated that the causes of her renal dysfunction are as follows: chronic interstitial nephritis caused by pseudo Bartter's syndrome resulting from chronic abuse of diuretics and purgatives, and Chinese herb nephropathy.