[Two Cases of Pseudo-Bartter Syndrome in Childhood: When to Suspect a Rare Onset Pattern of Cystic Fibrosis].

Cystic fibrosis is a multisystem disease with extremely variable onset, symptoms and course. One of the onset modality but also a complication of the disease is the pseudo-Bartter syndrome, characterized by hyponatremia, hypochloremic dehydration and metabolic alkalosis in absence of any renal disease. This syndrome occurs more frequently in the first year of life and has a peak in the summer. In this article, we describe two cases of cystic fibrosis associated with pseudo-Bartter syndrome in childhood. Excluding every possible cause of metabolic alkalosis associated with hyponatremia was crucial for our diagnostic pathway, and the experience gained with the first case helped a lot with the second one.

[Cystic fibrosis primarily presenting with pseudo-Bartter syndrome: a report of three cases and literature review]. / 以假性Bartter综合征为主要表现的囊性纤维化患儿3ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

OBJECTIVES: To summarize the clinical characteristics and genetic variations in children with cystic fibrosis (CF) primarily presenting with pseudo-Bartter syndrome (CF-PBS), with the aim to enhance understanding of this disorder. METHODS: A retrospective analysis was performed on the clinical data of three children who were diagnosed with CF-PBS in Hunan Children's Hospital from January 2018 to August 2023, and a literature review was performed. RESULTS: All three children had the onset of the disease in infancy. Tests after admission showed hyponatremia, hypokalemia, hypochloremia, and metabolic alkalosis, and genetic testing showed the presence of compound heterozygous mutation in the CFTR gene. All three children were diagnosed with CF. Literature review obtained 33 Chinese children with CF-PBS, with an age of onset of 1-36 months and an age of diagnosis of 3-144 months. Among these children, there were 29 children with recurrent respiratory infection or persistent pneumonia (88%), 26 with malnutrition (79%), 23 with developmental retardation (70%), and 18 with pancreatitis or extrapancreatic insufficiency (55%). Genetic testing showed that c.2909G>A was the most common mutation site of the CFTR gene, with a frequency of allelic variation of 23% (15/66). CONCLUSIONS: CF may have no typical respiratory symptoms in the early stage. The possibility of CF-PBS should be considered for infants with recurrent hyponatremia, hypokalemia, hypochloremia, and metabolic alkalosis, especially those with malnutrition and developmental retardation. CFTR genetic testing should be performed as soon as possible to help with the diagnosis of CF.

Cystic fibrosis and CFTR-related disorder with electrolyte imbalance at diagnosis: clinical features and outcome in an Italian cohort.

There is limited information available on the clinical data, sweat test trends, and outcomes of individuals with cystic fibrosis (CF) who present with an isolated episode of hypoelectrolytemia with metabolic alkalosis (HMA). This study describes a cohort of Italian individuals with HMA as presenting symptom. The study is a retrospective multicenter analysis of individuals who presented with HMA as an initial symptom and was followed at 8 Italian CF Centers, from March 1988 to March 2022. Demographic, clinical, microbiological, biochemical, and genetic data were extracted from local health records. Ninety-three individuals were enrolled in the study. At first evaluation, 82 (88.2%) were diagnosed with CF, and 11 received a CFTR-Related Disorder (CFTR-RD) diagnostic label. Twenty-three (85.1%) out of the 27 subjects who underwent CF neonatal screening (NBS) resulted falsely negative. After a mean observational period of 11.5 years, most of subjects had a mild pulmonary phenotype, pancreatic sufficiency, and rarely CF-related complications. Four CFTR-RD changed to a CF diagnosis during the study period, resulting in 86 (92.4%) subjects classified as CF. CONCLUSIONS:  Most CF patients presenting with isolated HMA have a mild course of disease and rarely CF-related complications. WHAT IS KNOWN: • Isolated episode of hypoelectrolytemia with metabolic alkalosis is a well-known onset symptom of Cystic Fibrosis in infancy. • There is limited information available on the clinical data and outcomes of individuals with Cystic Fibrosis who present with electrolyte imbalance at diagnosis. WHAT IS NEW: • Most patients with Cystic Fibrosis presenting with isolated hypoelectrolytemia and metabolic alkalosis have a mild course of disease and rarely CF-related complications. • Electrolyte imbalance at diagnosis of Cystic Fibrosis is a common symptom in children not screened for CF at birth, or in those who received a false negative result from newborn screening.

A Novel Mutation in Cystic Fibrosis Presenting as Pseudo Bartter Syndrome: A Case Report.

Pseudo-Bartter's (PB) syndrome is characterized by hypokalemic metabolic alkalosis and failure to thrive which constitutes a rare but typical presentation of cystic fibrosis (CF) in children. The most common mutation of CF is F508del, due to loss of 3 base pairs, causing deletion of phenylalanine, at position 508. We present a case of CF presenting with failure to thrive, dehydration, PB syndrome associated with urosepsis and primo-colonization with Escherichia coli suggesting the role of epigenetic factors. The heterozygous state for Phe508del mutation in Exon 11 combination with Glu92Ala in Exon 4 resulted in epigenetic effect on atypical phenotype as PBS, a novel mutation identified in our case.

Bartter Syndrome-Related Variants Distribution: Brazilian Data and Its Comparison with Worldwide Cohorts.

BACKGROUND: Genetic testing is recommended for accurate diagnosis of Bartter syndrome (BS) and serves as a basis for implementing specific target therapies. However, populations other than Europeans and North Americans are underrepresented in most databases and there are uncertainties in the genotype-phenotype correlation. We studied Brazilian BS patients, an admixed population with diverse ancestry. METHODS: We evaluated the clinical and mutational profile of this cohort and performed a systematic review of BS mutations from worldwide cohorts. RESULTS: Twenty-two patients were included; Gitelman syndrome was diagnosed in 2 siblings with antenatal BS and congenital chloride diarrhea in 1 girl. BS was confirmed in 19 patients: BS type 1 in 1 boy (antenatal BS); BS type 4a in 1 girl and BS type 4b in 1 girl, both of them with antenatal BS and neurosensorial deafness; BS type 3 (CLCNKB mutations): 16 cases. The deletion of the entire CLCNKB (1-20 del) was the most frequent variant. Patients carrying the 1-20 del presented earlier manifestations than those with other CLCNKB-mutations and the presence of homozygous 1-20 del was correlated with progressive chronic kidney disease. The prevalence of the 1-20 del in this BS Brazilian cohort was similar to that of Chinese cohorts and individuals of African and Middle Eastern descent from other cohorts. CONCLUSION: This study expands the genetic spectrum of BS patients with different ethnics, reveals some genotype/phenotype correlations, compares the findings with other cohorts, and provides a systematic review of the literature on the distribution of BS-related variants worldwide.

Acute Kidney Injury with Severe Metabolic Alkalosis Caused by Habitual Vomiting in an Alcohol Abuser with Pyloric Stenosis.

A 47-year-old man was complaining of consciousness disorder. He had acute kidney injury, hypokalemia, and severe metabolic alkalosis. Initial treatment using intravenous infusion of 0.9% saline and potassium chloride improved his consciousness. It was clarified that he was a severe alcohol abuser who habitually self-vomited. We diagnosed him with volume depletion and pseudo-Bartter's syndrome due to loss of chloride by habitual vomiting. Gastrointestinal endoscopy demonstrated pyloric stenosis, which was ameliorated by Helicobacter pylori eradication therapy. We should consider volume depletion and pseudo-Bartter's syndrome as differential diagnoses when we encounter patients with acute kidney injury and severe metabolic alkalosis.

Pseudo Bartter Syndrome in anorexia nervosa.

INTRODUCTION: Anorexia nervosa is a psychiatric disorder with various non-psychiatric manifestations that arise from the self-imposed malnourishment and possible purging behaviors. These medical manifestations or complications may mimic non psychiatric disorders and difficult the diagnosis of an eating disorder. CASE REPORT: We report the case of a patient with a binge-eating/purging subtype of anorexia nervosa, whose purges consisted in diuretic abuse. She kept her purges secret and during more than 1 year she was admitted several times in the emergency room for, sometimes life-threatening, hypokalemia. Furthermore, she consulted practitioners from different specialties and was hospitalized in a nephrology service to investigate chronic hypokalemia and other metabolic and hydroelectrolytic disturbances. A Bartter Syndrome was suspected, and she underwent genetic testing. Eventually she started psychiatric follow up and was admitted as an inpatient under the care of a specialized eating disorders unit. CONCLUSION: This patient presented a series of metabolic disturbances secondary to the diuretic abuse, that mimicked the manifestations of hereditary tubulopathies like Bartter Syndrome. Coincidentally it was found that the patient had a mutation in a gene linked to Bartter Syndrome, that wasn't enough to justify this diagnosis. So, a Pseudo Bartter Syndrome secondary to the diuretic abuse was evident. The focus on medical manifestations delayed the recognition of the anorexia nervosa and the associated diuretic abuse as the main cause of the electrolyte and metabolic disturbances. This case emphasizes the importance of being familiarized with the non-psychiatric manifestations of eating disorders, so they may be rapidly recognized and managed. LEVEL OF EVIDENCE: Level V, Case Report.

Characteristics of electrolyte imbalance and pseudo-bartter syndrome in hospitalized cystic fibrosis children and adolescents.

INTRODUCTION: Pseudo-Bartter syndrome (PBS) is a rare manifestation of Cystic fibrosis (CF) and can often be the initial presentation in these patients, however, due to significantly overlapping symptoms it is often misdiagnosed as simple dehydration or Bartter syndrome. The objective of our study was to highlight the key features of PBS and electrolyte imbalance in CF patients helping in early and prompt diagnosis. METHOD: We performed a retrospective study from January 2015 to December 2019 at the Aga Khan University Hospital (AKUH), Pakistan. CF patients aged from 1-18 years, admitted at AKUH were enrolled and their laboratory data and individual charts were reviewed. Patients were categorized into three groups based on their serum electrolyte profile and their clinical findings were compared. RESULT: We enrolled 72 CF patients, out of which 42 (58%) were categorized into the Normal Electrolyte (NE) group, 19 (26%) into the Electrolyte Imbalance (EI) group and 11 (15%) in the PBS group. Out of 11 cases, 6 (54.54%) patients in PBS group presented with features consistent with PBS leading to CF diagnosis labeled as "early presenters". Mean age of patients in the PBS group was 3.81± 0.86 years and their age at diagnosis were significantly lower as compared to other groups. Gastrointestinal disturbances including diarrhea, vomiting and constipation were more common in the EI and PBS groups. Polyuria was most common in the PBS (72%) group. Length of hospital stay showed no significant difference. CONCLUSION: Pseudo-Bartter syndrome can be a presenting feature of cystic fibrosis. Electrolyte imbalance should be anticipated in hospitalized CF children and adolescent.

[Food protein-induced enterocolitis syndrome in a patient with pseudo-Bartter syndrome associated with cystic fibrosis. A case report]. / Enterocolitis inducida por proteínas alimentarias en un paciente con síndrome de pseudo-Bartter asociado a fibrosis quística. Reporte de un caso.

INTRODUCTION: Food protein-induced enterocolitis is a non-immunoglobulin E-mediated food allergy with acute manifestations like recurrent vomiting, dehydration, and shock. It is a rare pathology that requires a high index of suspicion. Pseudo-Bartter syndrome (metabolic alkalosis, hypokalemia and hypochloremia in the absence of tubulopathy) is an infrequent complication of cystic fibrosis. CASE REPORT: A 5-month-old boy with recurrent vomiting, dehydration, and shock; who had been breastfed and had consumed baby formula three hours prior to the onset of symptoms. Laboratory tests confirmed hyponatremia, hypochloremic metabolic alkalosis, and hypokalemia in absence of tubulopathy; two iontophoresis showed altered results, stool elastase was decreased, and genetic sequencing confirmed the diagnosis of cystic fibrosis. The provocation test confirmed food protein-induced enterocolitis syndrome. CONCLUSION: Recurrent vomiting and dehydration after the intake of milk formula must lead to suspicion of food protein-induced enterocolitis syndrome. If pseudo-Bartter syndrome is found, cystic fibrosis must be ruled out.

Introducción: La enterocolitis inducida por proteínas alimentarias es una alergia alimentaria no mediada por inmunoglobulina E, manifestada en forma aguda por vómito recurrente, deshidratación y choque. Es una patología inusual que requiere alto índice de sospecha. El pseudo-Bartter (alcalosis metabólica, hipocaliemia e hipocloremia en ausencia de tubulopatía) es una complicación infrecuente de fibrosis quística. Reporte de caso: Niño de cinco meses de edad con vómito recurrente, deshidratación y choque, alimentado con lactancia materna, pero que consumió fórmula tres horas previas al inicio de síntomas. Los exámenes de laboratorio confirmaron hiponatremia, alcalosis metabólica hipoclorémica e hipocalemia sin tubulopatía; dos iontoforesis mostraron resultados alterados; la elastasa en materia fecal se encontró disminuida y la secuenciación genética confirmó el diagnóstico de fibrosis quística. La prueba de provocación confirmó enterocolitis inducida por proteínas alimentarias. Conclusión: El vómito recurrente y la deshidratación tras la ingesta de fórmula láctea deben hacer sospechar un enterocolitis inducida por proteínas alimentarias. Ante el hallazgo de pseudo-Bartter se debe descartar fibrosis quística.

A neonate with intrauterine growth restriction and pseudo-Bartter syndrome due to severe maternal eating disorder: A case report.

Maternal diet before and during pregnancy plays an important role for the developing fetus. Any eating disorder in this period can cause transient or/and permanent negative effects on the mother and her offspring.

Dehydrated patient without clinically evident cause: A case report.

BACKGROUND: Patients affected by cystic fibrosis can present with metabolic alkalosis such as Bartter's syndrome. In this case report we want to underline this differential diagnosis and we aimed focusing on the suspect of cystic fibrosis, also in case of a negative newborn screening. CASE SUMMARY: In a hot August -with a mean environmental temperature of 36 °C- an 8-mo-old female patient presented with severe dehydration complicated by hypokalemic metabolic alkalosis, in absence of fever, diarrhea and vomiting. Differential diagnosis between cystic fibrosis and tubulopathies causing metabolic alkalosis (Bartter's Syndrome) was considered. We started intravenous rehydration with subsequent improvement of clinical conditions and serum electrolytes normalization. We diagnosed a mild form of cystic fibrosis (heterozygous mutations: G126D and F508del in the cystic fibrosis transmembrane conductance regulator gene). The trigger factor of this condition had been heat exposure. CONCLUSION: When facing a patient with hypokalemic metabolic alkalosis, cystic fibrosis presenting with Pseudo-Bartter's syndrome should be considered in the differential diagnosis, even if the newborn screening was negative.

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.

Sodium Status and Replacement in Children and Adults Living with Cystic Fibrosis: A Narrative Review.

Patients with cystic fibrosis (CF) have a two- to four-fold higher sodium chloride sweat content compared with healthy controls. This high sweat salt loss increases the risk for electrolyte disturbances, associated with subacute or chronic complications. Sodium status therefore needs to be adequately monitored and salt intake adjusted to individual needs. The lack of current evidence to formulate specific recommendations and assess sodium status is reflected in a variability of recommendations in international guidelines. This narrative review presents an overview of the current evidence. Infants with CF in particular are at risk for severe sodium deficiency, potentially leading to metabolic alkalosis due to low intake and high sweat losses. More research on the assessment of sodium status and efficacy of sodium chloride supplements in the population of patients with CF, especially given the changing era of CF transmembrane conductance regulator modulatory treatment, is warranted.

Clinical features and accompanying findings of Pseudo-Bartter Syndrome in cystic fibrosis.

BACKGROUND: Pseudo-Bartter syndrome (PBS) is a rare complication of cystic fibrosis (CF) and there are limited data in the literature about it. We aimed to compare clinical features and accompanying findings of patients with PBS in a large patient population. METHODS: The data were collected from the Cystic Fibrosis Registry of Turkey where 1170 CF patients were recorded in 2017. Clinical features, diagnostic test results, colonization status, complications, and genetic test results were compared in patients with and without PBS. RESULTS: Totally 1170 patients were recorded into the registry in 2017 and 120 (10%) of them had PBS. The mean age of diagnosis and current age of patients were significantly younger and newborn screening positivity was lower in patients with PBS (P < .001). There were no differences between the groups in terms of colonization status, mean z-scores of weight, height, BMI, and mean FEV1 percentage. Types of genetic mutations did not differ between the two groups. Accompanying complications were more frequent in patients without PBS. CONCLUSION: PBS was detected as the most common complication in the registry. It could be due to warm weather conditions of our country. It is usually seen in younger ages regardless of mutation phenotype and it could be a clue for early diagnosis of CF.