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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 1  |  Page : 1-10

Clinical and laboratory study of infants and children with Bartter syndrome attending Alexandria University Children’s Hospital (10 years experience)


1 Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt
2 Department of Clinical and Chemical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Date of Submission20-Nov-2016
Date of Acceptance15-Feb-2017
Date of Web Publication12-Jul-2017

Correspondence Address:
Hanan M Fathy
Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, 01666
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJOP.AJOP_2_17

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  Abstract 

Background Bartter syndrome (BS) is a group of inherited, salt-losing tubulopathies presenting as metabolic alkalosis with normotensive hyperreninemia and hyperaldosteronism. It is a consequence of abnormal function of the kidneys, which become unable to properly regulate the volume and composition of body fluids because of defective reabsorption of NaCl in loop of Henle. A first consequence of the tubular defect in BS is polyuria, which is responsible for particular complications of pregnancy − that is, polyhydramnios and premature delivery. Low potassium levels in the blood may result from overactivity of the renin–angiotensin II–aldosterone hormone system that is essential in controlling blood pressure. To date, at least five genes have been linked to BS, and they characterize five types of BS.
Aim The aim of this work is to study the clinical and laboratory data of infants and children with BS attending Alexandria University Children’s Hospital during a 10-year period (January 2004–December 2013).
Participants and methods A retrospective analysis of children diagnosed with BS attending Alexandria University Children’s Hospital during a 10-year period (January 2004–December 2013) was carried out. On the basis of the clinical, biochemical features, and ultrasonographic findings, 20 children were diagnosed with BS. Their demographic, clinical, biochemical, and hormonal profiles were analyzed. Follow-up data and outcomes were recorded.
Results The majority of cases had perinatal history of polyhydraminos. All cases had high urinary chloride in spot urine analysis. The mainstay of treatment in BS is potassium supplementation and indomethacin. Correction of hypokalemia and hyperprostaglandinemia are mandatory for improving the symptoms (vomiting, polyuria) and chronic sequalae such as FTT and growth retardation.
Conclusions According to this study, BS should be suspected in any child with a history of failure to thrive and metabolic alkalosis. Early diagnosis and treatment with NSAIDs are life-saving.

Keywords: bartter syndrome, hypokalemia, hyperreninemia, hyperaldosteronism, hypercalciuria, hypomagnesemia, metabolic alkalosis, nephrocalcinosis


How to cite this article:
Thabet M, Sharaki OA, Fathy HM, Ayoub AZ. Clinical and laboratory study of infants and children with Bartter syndrome attending Alexandria University Children’s Hospital (10 years experience). Alex J Pediatr 2017;30:1-10

How to cite this URL:
Thabet M, Sharaki OA, Fathy HM, Ayoub AZ. Clinical and laboratory study of infants and children with Bartter syndrome attending Alexandria University Children’s Hospital (10 years experience). Alex J Pediatr [serial online] 2017 [cited 2018 Nov 13];30:1-10. Available from: http://www.ajp.eg.net/text.asp?2017/30/1/1/210438


  Introduction Top


Bartter syndrome (BS) was originally described by Bartter et al. in 1962 [1]. It is a primary tubulopathy that presents with failure to thrive (FTT), fatigue, polyuria, polydipsia, nocturia, generalized weakness, salt cravings, dehydration, vomiting, muscle weakness, muscle spasm, tetany, mental confusion, and short stature [2].

It is an inherited disorder (autosomal recessive) characterized by hypokalemia, hypochloremic metabolic alkalosis, hyperreninemia, hyperprostaglandinism, normal blood pressure, with an increased urinary loss of sodium (Na), chloride (Cl), potassium (K), calcium (Ca), and prostaglandins [3].

Epidemiology

BS is rare, and estimates of its occurrence vary from country to country. In the USA, the estimated prevalence is one per million [4].

In Kuwait, the prevalence in the general population is 1.7 cases per 100 000 persons. In Palestine, evaluation of an affected family member (12) revealed phenotypic features of both Gitelman syndrome and classic BS, whereas in United Arab Emirates two cases of BS among nationals were observed. In Saudi Arabia, nine patients (the father and eight siblings) had biochemical features of BS [5].

In Egypt, there is no estimated prevalence of BS.

Pathophysiology

Thick ascending loop of Henle (TALH) has channels, coded by a specific gene. Any mutation in the gene results in impaired channel function and hence defective electrolyte reabsorption (Na+ K+, Cl, and Ca2+) in the TALH and delivery of large volumes of urine with a high content of Na+, K+, Cl, and Ca2+ to the distal tubule [6],[7]. In the distal tubule, part of the delivered Na+ will be reabsorbed in exchange for intracellular K+. Hence, K wasting occurs [8]. Impaired Na absorption in TALH will result in increased levels of prostaglandin E2. Increased PGE2 will exacerbate primary defect of Cl transport in TALH, which will stimulate renin–angiotensin–aldosterone axis causing hypokalemia (because of hyperaldosteronism), and impede water reabsorption in collecting ducts leading to hyposthenuria. Hyperaldosteronism increases K wasting and stimulates exchange of intracellular H ions for K ions for intraluminal K (distal tubule and collecting duct) resulting in exaggeration of metabolic alkalosis [9],[10].

Etiology and types

BS is a hereditary disease, with an autosomal recessive (BS types I–IV) or autosomal dominant (BS type V) mode of transmission [11]. To date, at least five genes have been linked to BS, and they characterize five types of BS [12] ([Table 1]).
Table 1 Genetics and presentation (clinical and lab) of Bartter syndrome [13]

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Clinical presentation

Most cases of BS are usually symptomatic early in life, although occasional patients (mostly BS type III and rare patients with BS types IV and V) may continue into adulthood with few, if any, manifestations [11].

Mothers of fetus with BS often present with unexplained polyhydramnios between 24 and 30 weeks of gestation. Intrauterine growth restriction may also be associated with the inability of the kidney tubule to retain salt and water, resulting in fetal polyuria. Infants are usually born preterm [8],[10],[14].

After birth, rapid weight loss, lethargy and poor feeding, FTT, fatigue, polyuria, polydipsia, nocturia, generalized weakness, salt cravings, dehydration, vomiting, muscle weakness, muscle spasm, tetany, mental confusion, and short stature (if untreated) were observed [2],[15],[16],[17],[18].

Facial features such as triangular face, prominent forehead, large eyes, protruding ears, and drooping mouth may be present. Sensorineural deafness is seen in type IV BS. Strabismus, convulsions, and increased susceptibility to infections are also reported [19],[20].

Patients with antenatal BS (types I and II) fail to establish an adequate transepithelial voltage gradient to drive Ca and magnesium absorption, giving rise to hypercalciuria and hypermagnesiuria, which increase predisposition to nephrocalcinosis [21].

Clinically, BS types III and V appear to be less severe than types I, II, and IV despite similar biochemical indices [22].

Untreated infants fail to thrive and may die in a few days as a result of dehydration, poor feeding, or severe electrolyte disturbance. Mild mental retardation is linked to delay in diagnosis and treatment [18].

Complications

The important complications of BS include hypercalciuria leading to nephrocalcinosis, growth retardation, FTT, and developmental delay in untreated patients. Sensorineural deafness is associated with BS IV. Cardiac arrhythmia and sudden death may result from electrolyte imbalances. There was a significant decrease in bone mineral density. Very rarely progressive renal disease, renal failure, and interstitial nephritis can occur. Acute renal failure from rhabdomyolysis due to hypokalemia has also been reported [9],[23],[24],[25].

Diagnosis

The diagnosis of BS is largely one of exclusion, made in patients who present with unexplained hypokalemia and metabolic alkalosis with a normal or low blood pressure, and in whom other, more common, etiologies are ruled out.

The most helpful laboratory test is measurement of the urine Cl concentration, which is usually greater than 40 mmol/l in patients with BS in whom Cl excretion is equal to dietary Cl intake [26].

Measurement of urinary Ca excretion, which is usually high-normal or elevated in patients with BS, is another diagnosis method. Urinary Ca excretion can be determined with a 24 h urine collection or estimated from the calcium-to-creatinine (Ca/Cr) ratio in a spot urine specimen. The range of normal values for these measurements is more than 4 mg/kg/day or more than 0.21 urinary Ca/Cr ratio [27].

Prenatal diagnosis can be made by the high Cl content of the amniotic fluid [28],[29],[30] and mutational analysis of genomic DNA extracted from cultured amniocytes obtained by amniocentesis [31].

Differential diagnosis

The main differential diagnosis is with Gitelman syndrome, also known as the hypocalciuric variant of BS. Gitelman syndrome is an autosomal recessive disorder that presents with hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and normal blood pressure [32],[33],[34],[35].

In contrast to the typically early clinical presentation in BS, Gitelman syndrome is usually not diagnosed until late childhood or adulthood [33], although presentation in infancy has been described [36].

Other causes of unexplained hypokalemia and metabolic alkalosis associated with a normal or low blood pressure must be excluded before making the diagnosis of BS or Gitelman syndrome. The most common disorders that have a similar presentation and must be excluded are unexplained vomiting and diuretic use. It is not uncommon for patients to have both vomiting and diuretic abuse.

Measurement of the urine Cl concentration usually distinguishes unexplained self-induced vomiting from BS and Gitelman syndrome [26],[37].

The urine Cl concentration is usually less than 25 mmol/l in patients with vomiting due to both hypovolemia and hypochloremia. In contrast, the urine Cl concentration is typically much higher (usually >40 mmol/l) in patients with BS or Gitelman syndrome [26].

In the case of long use of diuretics, appropriate drug history and demonstration of the diuretic in the urine will establish the diagnosis [38],[39].

Other disorders that cause volume depletion but do not affect renal tubular function can partially mimic BS. These conditions have sometimes been called ‘pseudo-BS’ including cyclic vomiting, congenital Cl diarrhea, cystic fibrosis, and pyloric stenosis.

Management

The tubular defects in BS or Gitelman syndrome cannot be corrected. As a result, treatment, which must be life-long, is aimed at minimizing the effects of the secondary increases in prostaglandin, renin, and aldosterone production and at correcting the volume deficit and electrolyte abnormalities.

The primary aim of the treatment of BS is correction of hypokalemia and alkalosis. Therefore, administration of KCl is always necessary. The dose of KCl supplementation should individually be titrated in accordance with the patient’s needs and must balance the amount lost by the kidney. However, this mode of supplementation therapy is almost totally ineffective by itself, as administered K is lost through the kidney in a short period of time [40].

K-sparing agents such as spironolactone or triamterine would be an effective additive to supplementation therapy at this stage. Indeed, these groups of medication offer an effective but transient control of hypokalemia [40].

Neutralizing the amplification effect of prostaglandins on the features of BS has long been the mainstay of drug therapy of this syndrome. Prostaglandin synthetase inhibitors are the main group of drugs recommended in this respect. Among many prostaglandin synthetase inhibitors, indomethacin is the most widely used [41].

The recommended dose of indomethacin is 2–3 mg/kg/day in two or three divided doses. Indomethacin decreases salt wasting and the degree of hypokalaemic alkalosis, and also partially corrects the impaired urine concentrating ability [42].

Other drugs used are acetylsalicylic acid (100 mg/kg/day), ibuprofen (30 mg/kg/day), or ketoprofen (20 mg/kg/day).

Renal transplantation has primarily been performed in isolated case reports of patients who developed end-stage renal disease because of coexisting renal disease or because of complications related to volume depletion, electrolyte abnormalities, drug-related side effects, and/or nephrocalcinosis. Renal transplantation should correct the transport abnormalities in BSs. Recurrence of the disease in the transplanted kidney should not occur and has not been described [43],[44],[45].


  Aim Top


The aim of this work was to study the clinical and laboratory data of infants and children with BS attending Alexandria University Children’s Hospital (AUCH) during a 10-year period (January 2004–December 2013).


  Participants and methods Top


Study design

A retrospective study was used. Ethics committee approval has been obtained before starting the study.

Study setting

The study was carried out at the nephrology clinic in the AUCH.

Target population

The target population of the study was BS cases attending the nephrology clinic at the AUCH.

Sampling design

Sampling

All records of patients diagnosed as BS in AUCH from 2004 to 2013 were reviewed. Only 20 patients were identified and fulfilled the criteria of BS.

Data collection methods

The following data were collected from patient files:
  1. Personal characteristics:
    1. File number and sex.
    2. Date of birth and time of presentation of the child.
    3. Consanguinity, perinatal history, and family history of a similar condition.
  2. Initial clinical presentation:
    1. The initial presentation such as polyuria, polydipsia, vomiting, FTT, recurrent dehydration, and developmental delay were recorded.
  3. Growth parameters:
    • Weight and height were collected from files. Child growth standards issued by the WHO [46] were used to classify the children’s weight for age, height for age, and weight for height in terms of a cutoff point of −2 SD below the median using growth reference curves. Children included in the study according to the above classification and who measured below −2 SD for the reference were considered growth retarded [46].
  4. Laboratory investigations:
    1. Initial biochemical findings (blood urea nitrogen, Cr, Ca, phosphorus, ALP, Cl, Na, K, uric acid).
    2. Arterial blood gases (pH, HCO3, PCO2).
    3. Spot urine analysis (Na, K, Cl, Ca/Cr ratio).
  5. Other investigations:
    1. Hearing assessment to identify cases of bilateral sensorineural hearing loss.
    2. Renal ultrasound (for nephrocalcinosis).
  6. Complications and outcome:
    1. Complications such as growth retardation and chronic renal impairment were collected from data.
    2. The results of some anthropometric measurements of BS cases at diagnosis and on follow-up visits were compared.
  7. Treatment:
    • K syrup, indomethacin, aldactone, and brufen were used.
    • Operational definitions:
    1. Hypokalemia: It is a condition in which the level of K in serum is below the normal serum range [47]

      • Newborn 3.7–5.9 mmol/l.
      • Infant 4.1–5.3 mmol/l.
      • Child 3.4–4.7 mmol/l.
    2. Hypochloremia: It is an electrolyte disturbance in which there is an abnormally decreased level of the Cl ion in the blood. The normal serum range for Cl is 97–107 mmol/l [48].
    3. Hypercalciuria: It is defined as more than 4 mg/kg/day or more than 0.21 urinary Ca/Cr ratio [27].

      Normal spot urine analysis values were defined as follows:

      • Cl 15–40 mmol/l [49]
      • K 20–60 mmol/l [50].
      • Na 20–230 mmol/l [50].



  Results Top


This study was conducted on cases of pediatric BS diagnosed at AUCH from January 2004 to December 2013. It included 20 patients.

As regards sex distribution, male patients represent 70% of total cases, making male-to-female ratio 2.3 : 1.

The average age of patients was 24 months (range: 1.0–132.0 months), whereas the average age at presentation was 2 months (range: 0.0–12.0 months).

Positive family history was found in 35% of cases, perinatal history of polyhydramnios was found in 70% of cases, whereas consanguinity of patients and parents was observed in 40% ([Table 2]).
Table 2 Distribution of Bartter syndrome cases according to personal data, perinatal history, family history, and consanguinity

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Out of all BS cases, 70% presented with recurrent dehydration, 45% with vomiting, 45% with FTT, and 15% with polyuria ([Figure 1]).
Figure 1 Distribution of Bartter syndrome cases according to their clinical presentation.

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[Figure 2] illustrates that the majority of patients were normotensive (70%), hypotensive (25%), and 5% of patients are hypertensive (one patient) according to blood pressure percentile for age and sex.
Figure 2 Distribution of Bartter syndrome cases according to blood pressure (mmHg).

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In the studied patient, it was found that average serum Na level was 124.5 mmol/l, average serum K was 2.03 mmol/l, average serum Cl was 78.5 mmol/l, average serum Ca was 9.15 mg/dl, and average serum magnesium was 1.9 mg/dl.

Arterial blood gas analysis of studied cases revealed that pH ranged from 7.5 to 7.73 with a mean of 7.6±0.1, serum HCO3 ranged from 32 to 45.2 mmol/l with a mean of 37.6±3.8, and serum PCO2 ranged from 22.0 to 47.2 mmHg with a mean of 30.6±7.5.

Regarding spot urine analysis, the mean urinary Na was 67.1±31.3 mmol/l, mean urinary K was 46.5±27.6 mmol/l, and mean urinary Cl was 82.2±36.5 mmol/l ([Table 3]).
Table 3 Distribution of Bartter syndrome cases according to initial biochemical findings

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It was found that 55% of patients have high Ca/Cr ratio, 30% of patients have normal Ca/Cr ratio, and 15% of patients have low Ca/Cr ratio ([Figure 3]).
Figure 3 Distribution of Bartter syndrome cases according to calcium-to-creatinine ratio.

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Basically all the patients were treated by K syrup. Most of the patients need other adjuvant treatments as follows: 45% indomethacin, 30% aldactone, 5%, brufen, and 5% minirin ([Figure 4]).
Figure 4 Distribution of treatment among Bartter syndrome cases.

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In this study, it was found that 55% of patients presented with severe symptoms, whereas 45% have mild symptoms ([Figure 5]).
Figure 5 Distribution of Bartter syndrome cases according to severity.

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[Table 4] illustrates that, among patients who presented early (<2 ms), 33.3% of children were underweight at presentation, whereas only 11.1% were underweight at follow-up. In addition, it shows that 22.2% of children were of short stature at presentation, whereas only 11.1% were of short stature at follow-up.
Table 4 Comparison between some anthropometric measurements at presentation and on follow-up visits in different age groups

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In the age group that presented late (>2 ms), 36.4% of children were underweight at presentation and 27.3% were underweight at follow-up visit, whereas 27.3% of children were of short stature at presentation and 18.2% were of short stature at follow-up visit.

In both groups, there was no significant statistical difference in patients’ growth parameters at presentation and on follow-up visits.

[Table 5] shows that there was a significant statistical difference in the patients’ growth parameters before and after receiving indomethacin.
Table 5 Comparison between some anthropometric measurements before and after receiving indomethacin

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In all, 44.4% were underweight before indomethacin treatment, whereas 22.2% were underweight after receiving indomethacin.

In all, 22.2% were of short stature before indomethacin treatment, with improvement of all patients after receiving indomethacin.

[Table 6] shows that all mild cases of BS survived, whereas 81.8% of severe cases survived with no significant statistical difference.
Table 6 Relation between severityof Bartter syndrome cases and fate, age at presentation, and response to medication

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It was observed that 54.5% of patients who presented early (<2 ms) had severe symptoms in comparison with 45.5% of patients who presented later (≥2 ms), with no significant statistical difference.

[Table 6] reveals that all patients of BS received K syrup, 63% of severe cases received indomethacin in comparison with 22.2% of mild cases, and 27.3% of severe cases received aldactone in comparison with 33% mild cases.

It was observed that 22.2% of patients who presented early (<2 ms) died, whereas no deaths were observed in patients who presented later (>2 ms) ([Table 7]).
Table 7 Relation between age at presentation and fate of Bartter syndrome cases

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  Discussion Top


BS is an autosomal recessive disorder with a characteristic set of metabolic abnormalities [51],[52]. These include hypokalemia, metabolic alkalosis, hyperreninemia, hyperplasia of the juxtaglomerular apparatus (the source of renin in the kidney), hyperaldosteronism, and, in some patients, hypomagnesemia [53].

This research included 14 male and six female patients, with a male : female ratio of 2.3 : 1.0. This observation is similar to a study conducted by Sampathkumar et al. [54], on seven children diagnosed as BS in India during an 8-year period from 2001 to 2009, which shows a male-to-female ratio of 3.0 : 1.0, whereas in the study by Abdel-Al et al. [55] in Kuwait had female predominance with a male-to-female ratio (1 : 1.6) and the stud by Dillon et al. [56] showed equal sex distribution.

The age of BS cases who attended the hospital ranged from 1 month to 11 years, with a median of 24 months. The mean age of patients was 9.3 months (range: 2–32 months) in the study conducted by Abdel-Al et al. [55].

Sampathkumar et al. [54] revealed that age of patients ranged from 2 to 15 months, with the mean age of 6.45 months. Mean age at presentation was 3.0±4.0 months, which is close to the results of Dillon et al. [56]. Delayed diagnosis may be due to lack of awareness of renal tubular diseases (RTD) among general physicians and to a lesser extent to lack of diagnostic facilities, especially for the underlying metabolic diseases. In the present studied group, consanguinity rate was 40% and positive family history was observed among only 35% of cases. In the study by Abdel-Al et al. [55], both consanguinity and familial history among the patients were high (69 and 54%, respectively). Parental consanguinity rate in India is reported to be around 28.5% [54]. The significant difference in the consanguinity rate in RTD may be due to the autosomal recessive inheritance characteristics of the most common tubular disorders [57].

It was found that perinatal history of polyhydramnios is positive in 70% of our studied patients. Shalev et al. [58] from Israel analyzed retrospectively the data from 13 infants with BS and nerve deafness who were born during a 20-year period. They found that all pregnancies were complicated by polyhydramnios and premature birth [58], whereas polyhydramnios and prematurity were present in two (28.5%) patients in the study conducted by Sampathkumar et al. [54].

The most common presenting symptoms were recurrent dehydration (70%), vomiting (45%), FTT (48%), and polyuria (44%). The most common presenting symptoms varied in different literatures. Polyuria/dehydration (33%) and growth retardation (25%) were the most common presenting symptoms explained by Zelikovic et al. [22]. The most common symptoms noticed in Sampathkumar et al. [54] study were FTT (85.7%), vomiting (57%), and dehydration (57%).

The present study shows that the majority of cases (70%) are normotensive according to blood pressure percentile for age and sex; Sampathkumar et al. [54] found that all patients are normotensive.

Hypokalemia was a constant feature among patients of BS (100%). Hypochloremia and metabolic alkalosis are also noticed in 100% of patients with BS. The studies by Sampathkumar et al. [54] and Abdel-Al et al. [55] also showed hypokalemia and hypochloremia in all the patients.

Hyperreninemia was present in 100% of patients, whereas hyperaldosteronism was present in 83.4% (one patient had normal aldosterone level). This may be due to lab error. The studies by Sampathkumar et al. [54] and Abdel-Al et al. [55] also showed hyperreninemia and hyperaldosteronism in all the patients.

Hypercalciuria and nephrocalcinosis were described in the study by Garel et al. [59] which recorded hypercalciuria in 33% and nephrolithiasis in 8%. In present study, hypercalciuria was found in 55% of studied patients, but no data were available about nephrocalcinosis. Hypocalciuria (urinary Ca/Cr ratio between 0.01 and 0.10) [60] was found in 30% of patients.

At the nephrology unit of AUCH, the mainstay of therapy in BS cases is K replacement. In all, 100% of studied cases receive K supplementation, but only 30% receive aldactone.

Most of our patients (45%) need another adjuvant therapy, which is considered now as a cornerstone medication in the management of BS. Among prostaglandin synthetase inhibitors, indomethacin is the most widely used [7],[61],[62],[63],[64].

Dillon et al. [56] used indomethacin in 60% of his patients. Similarly, 63% of severe cases in the present study received indomethacin, whereas Abdel-Al et al. [55] used it in all cases diagnosed as BS.

After successful therapy, a relative improvement in anthropometric measurements of the patients was observed. However, it was not statistically significant. However, in patients who received indomethacin, there was a significant catch-up growth when compared with a sex- and age-matched normal population. Abdel-Al et al. [55] showed significant catch-up growth in 30.76% of patients, whereas the study by Dillon et al. [56] showed catch-up growth in all patients treated with indomethacin therapy with remarkable clinical and biochemical improvement [56].

As regards the long-term prognosis, usually prognosis in many cases is good, with patients being able to lead a fairly normal life [65]. The death rate was 10% of total cases (two patients), which is close to that in the study by Abdel-Al et al. [55], 7.69% (one patient).

Genetic studies were not conducted in any of our children because of nonavailability of such specialized laboratories in our region. There is no direct correlation between the clinical phenotype and the underlying genotypic abnormality, even with well-characterized defects in a single transporter. However, more severe and earlier clinical manifestations may be seen with mutations leading to defects in Na–K–2Cl cotransporter and the luminal K channel [66].

There were no available data about cases that are complicated by renal failure or nephrocalcinosis.


  Conclusion Top


From this study we concluded the following:
  1. BS is an uncommon RTD.
  2. The majority of cases had perinatal history of polyhydraminos.
  3. The most common presenting symptoms were recurrent dehydration (70%), vomiting (45%), FTT (45%), and polyuria (15%).
  4. The majority of BS cases were normotensive.
  5. All cases had metabolic alkalosis, hypokalemia, and hypochloremia.
  6. All cases had high urinary Cl in spot urine analysis.
  7. Although all cases were spotted early and adequately treated, as evidenced by improvement of symptomatology and lab parameters, yet this did not show significant statistical difference as regards improvement in growth parameter during follow-up.
  8. The mainstay of treatment in BS is K supplementation and indomethacin.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Bartter FC, Pronove P, Gill JR Jr, MacCardle RC. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis: a new syndrome. Am J Med 1962; 33:811–828.  Back to cited text no. 1
[PUBMED]    
2.
Rodríguez-Soriano J. Bartter and related syndromes; the puzzle is almost solved. Pediatr Nephrol 1998; 12:315–327.  Back to cited text no. 2
    
3.
Bartter FC, Pronove P, Gill JR Jr et al. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome. Am J Med 1962; 33:811–828.  Back to cited text no. 3
    
4.
Almeida AJ, Burg MB. Sodium transport in the rabbit connecting tubule. Am J Physiol 1982; 243:F330–F334.  Back to cited text no. 4
    
5.
Lang F, Rehwald W. Potassium channels in renal epithelial and hypokalemic alkalosis. A new syndrome. Physiol Rev 2002; 72:1–21.  Back to cited text no. 5
    
6.
Brochard K, Boyer O, Blanchard A, Loirat C, Niaudet P, Macher MA et al. Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome. Nephrol Dial Transplant 2009; 24:1455–1464.  Back to cited text no. 6
    
7.
Seyberth HW, Schlingmann KP. Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects. Pediatr Nephrol 2011; 26:1789–1802.  Back to cited text no. 7
    
8.
Proesmans W. Bartter syndrome and its neonatal variant. Eur J Pediatr 1997; 156:669–679.  Back to cited text no. 8
    
9.
Dell KM, Avner ED. Bartter–Gitelman syndromes and other inherited tubular transport abnormalities. In: Kleigman RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson textbook of pediatrics. 18th ed. Philadelphia, PA: Saunders; 2007:2201–2202.  Back to cited text no. 9
    
10.
Bhat YR, Vinayaka G, Vani R, Prashanth KA, Sreelakshmi K. Antenatal Bartter syndrome: a rare cause of unexplained severe polyhydramnios. Ann Trop Paediatr 2011; 31:153–157.  Back to cited text no. 10
    
11.
Simon DB, Karet FE, Hamdan JM. Bartter’s syndrome, hypokalemic alkalosis with hypercalciuria is caused by mutation in Na-K-2Cl cotransporter NKCC2. Nat Genet 1996; 13:183–188.  Back to cited text no. 11
    
12.
Peters M, Jeck N, Reinalter S, Leonhardt A, Tönshoff B, Klaus G et al. Clinical presentation of genetically defined patients with hypokalemic salt losing tubulopathies. Am J Med 2002; 112:183–190.  Back to cited text no. 12
    
13.
Hebert SC. Bartter syndrome. Curr Op Nephrol Hypertens 2003; 12:527–532.  Back to cited text no. 13
    
14.
Rodrigues Pereira R, Hasaart T. Hydramnios and observations in Bartter’s syndrome. Acta Obstet Gynecol Scand 1982; 61:477–478.  Back to cited text no. 14
    
15.
Colussi G. Bartter syndrome. Orphanet encyclopedia, 2005. Available at: http://www.orpha.net/data/patho/GB/uk-Bartter.pdf.  Back to cited text no. 15
    
16.
Massa G, Proesmans W, Devlieger H et al. Electrolyte composition of the amniotic fluid in Bartter syndrome. Eur J Obstet Gynecol Reprod Biol 1987; 24:335–340.  Back to cited text no. 16
    
17.
Ohlsson A, Sieck U, Cumming W, Akhtar M, Serenius F et al. A variant of Bartter’s syndrome. Bartter’s syndrome associated with hydramnios, prematurity, hypercalciuria and nephrocalcinosis. Acta Paediatr Scand 1984; 73:868–874.  Back to cited text no. 17
    
18.
Al-Shibli A, Yusuf M, Abounajab I, Willems PJ. Mixed Bartter-Gitelman syndrome: an inbred family with a heterogeneous phenotype expression of a novel variant in the CLCNKB gene. Springerplus 2014; 3:96.  Back to cited text no. 18
    
19.
Landau D, Shalev H, Ohaly M, Carmi R. Infantile variant of Bartter syndrome and sensorineural deafness: a new autosomal recessive disorder. Am J Med Genet 1995; 59:454–459.  Back to cited text no. 19
    
20.
Madrigal G, Saborio P, Mora F et al. Bartter syndrome in Costa Rica: a description of 20 cases. Pediatr Nephrol 1997; 11:296–301.  Back to cited text no. 20
    
21.
Oliver TF, James CMC. Understanding Bartter syndrome and Gitelman syndrome. World J Pediatr 2012; 8:25–30.  Back to cited text no. 21
    
22.
Zelikovic I, Szargel R, Hawash A, Labay V, Hatib I, Cohen N et al. A novel mutation in the chloride channel gene, CLCNKB, as a cause of Gitelman and Bartter syndromes. Kidney Int 2003; 63:24–32.  Back to cited text no. 22
    
23.
Bettinelli A, Borsa N, Bellantuono R, Syrèn M-L, Calabrese R, Edefonti A et al. Patients with biallelic mutations in the chloride channel gene CLCNKB: long-term management and outcome. Am J Kidney Dis 2007; 49:91–98.  Back to cited text no. 23
    
24.
Scognamiglio R, Negut C, Calo LA. Aborted sudden cardiac death in two patients with Bartter’s/Gitelman’s syndromes. Clin Nephrol 2007; 67:193–197.  Back to cited text no. 24
    
25.
Proesmans W, Devlieger H, van Assche A, Eggermont E, Vandenberghe K, Lemmens F et al. Bartter syndrome in two siblings − antenatal and neonatal observations. Int J Pediatr Nephrol 1985; 6:63–70.  Back to cited text no. 25
    
26.
Veldhuis JD, Bardin CW, Demers LM. Metabolic mimicry of Bartter’s syndrome by covert vomiting: utility of urinary chloride determinations. Am J Med 1979; 66:361.  Back to cited text no. 26
    
27.
Butani L, Kalia A. Idiopathic hypercalciuria in children − how valid are the existing diagnostic criteria? Pediatr Nephrol 2004; 19:577–582.  Back to cited text no. 27
    
28.
Rodriguez-Soriano J. Tubular disorders of electrolyte regulation. In: Avner E, Harmon W, Niaudet P, editors Pediatric nephrology. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2004:729–756.  Back to cited text no. 28
    
29.
Rodriguez-Soriano J. Bartter’s syndrome comes of age. Pediatrics 1999; 103:663–664.  Back to cited text no. 29
    
30.
Dane B, Dane C, Aksoy F. Antenatal Bartter syndrome: analysis of two cases with placental findings. Fetal Pediatr Pathol 2010; 29:121–126.  Back to cited text no. 30
    
31.
Norton ME, Merrill J, Cooper BAB. Neonatal complications after the administration of indomethacin for preterm labor. N Engl J Med 1993; 329:1602–1607.  Back to cited text no. 31
    
32.
Monnens L, Bindels R, Grünfeld JP. Gitelman syndrome comes of age. Nephrol Dial Transplant 1998; 13:1617–1619.  Back to cited text no. 32
    
33.
Bettinelli A, Bianchetti MG, Girardin E, Caringella A, Cecconi M, Appiani AC et al. Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes. J Pediatr 1992; 120:38–43.  Back to cited text no. 33
    
34.
Cruz DN, Shaer AJ, Bia MJ, Lifton RP, Simon DB; Yale Gitelman’s and Bartter’s Syndrome Collaborative Study Group. Gitelman’s syndrome revisited: an evaluation of symptoms and health-related quality of life. Kidney Int 2001; 59:710–717.  Back to cited text no. 34
    
35.
Cruz DN, Simon DB, Nelson-Williams C, Farhi A, Finberg K, Burleson L et al. Mutations in the Na-Cl cotransporter reduce blood pressure in humans. Hypertension 2001; 37:1458–1464.  Back to cited text no. 35
    
36.
Tammaro F, Bettinelli A, Cattarelli D, Cavazza A, Colombo C, Syrén ML et al. Early appearance of hypokalemia in Gitelman syndrome. Pediatr Nephrol 2010; 25:2179–2182.  Back to cited text no. 36
    
37.
Mitchell JE, Seim HC, Colon E, Pomeroy C et al. Medical complications and medical management of bulimia. Ann Intern Med 1987; 107:71.  Back to cited text no. 37
    
38.
D’Avanzo M, Santinelli R, Tolone C, Bettinelli A, Bianchetti MG. Concealed administration of frusemide simulating Bartter syndrome in a 4.5 year-old boy. Pediatr Nephrol 1995; 9:749–750.  Back to cited text no. 38
    
39.
Mersin SS, Ramelli GP, Laux-End R, Bianchetti G. Urinary chloride excretion distinguishes between renal and extrarenal metabolic alkalosis. Eur J Pediatr 1995; 154:979–982.  Back to cited text no. 39
    
40.
Chaimovitz C, Levi J, Better OS, Oslander L, Benderli A. Studies on the site of renal salt loss in a patient with Bartter’s syndrome. Pediatr Res 2003; 7:89–94.  Back to cited text no. 40
    
41.
Verberckmoes R, van Damme BB, Clement J. Bartter’s syndrome with hyperplasia of renomedullary cells: successful treatment with indomethacin. Kidney Int 1976; 9:302–307.  Back to cited text no. 41
    
42.
Vaisbich MH, Fujimura MD, Koch VH. Bartter syndrome: benefits and side effects of long-term treatment. Pediatr Nephrol 2004; 19:858–863.  Back to cited text no. 42
    
43.
Calò LA, Marchini F, Davis PA, Rigotti P, Pagnin E, Semplicini A. Kidney transplant in Gitelman’s syndrome. Report of the first case. J Nephrol. 2003; 16:144–147.  Back to cited text no. 43
    
44.
Kim JY, Kim GA, Song JH, Lee SW, Han JY, Lee JS, Kim MJ. A case of living-related kidney transplantation in Bartter’s syndrome. Yonsei Med J 2000; 41:662–665.  Back to cited text no. 44
    
45.
Takahashi M, Yanagida N, Okano M, Ishizaki A, Meguro J, Kukita K et al. A first report: living related kidney transplantation on a patient with Bartter’s syndrome. Transplant Proc 1996; 28:1588.  Back to cited text no. 45
    
46.
WHO. The WHO child growth standards. Geneva, Switzerland: World Health Organization; 2006.  Back to cited text no. 46
    
47.
Kratz A, Ferraro M, Sluss PM, Lewandrowski KB et al. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Laboratory reference values. N Engl J Med 2004;351:1548–1563.  Back to cited text no. 47
    
48.
Cambier C, Detry B, Beerens D, Florquin S, Ansay M, Frans A, Clerbaux T, Gustin P. Effects of hyperchloremia on blood oxygen binding in healthy calves. J Appl Physiol 1998;85:1267–1272.  Back to cited text no. 48
    
49.
Sherman RA, Eisinger RP. The use (and misuse) of urinary sodium and chloride measurements. JAMA 1982;247:3121–3124.  Back to cited text no. 49
    
50.
Fischbach F, Dunning MB. A manual of laboratory and diagnostic tests. 9th ed. Philadelphia, PA: Wolters Kluwer Health; 2015.  Back to cited text no. 50
    
51.
Srivastava RN, Bagga A. Renal tubular disorders. In: Srivastava RN, Bagga A, editors. Pediatric nephrology. 4th ed. New Delhi, India: Jaypee Brothers Publishers; 2005:278–279.  Back to cited text no. 51
    
52.
Konrad M, Weber S. Recent advances in molecular genetics of hereditary magnesium-losing disorders. J Am Soc Nephrol 2003; 14:249–260.  Back to cited text no. 52
    
53.
Naesens M, Steels P, Verberckmoes R, Vanrenterghem Y, Kuypers D. et al.. Bartter’s and Gitelman’s syndromes: from gene to clinic. Nephron Physiol 2004; 96:65–78.  Back to cited text no. 53
    
54.
Sampathkumar K, Muralidharan U, Kannan A, Ramakrishnan M, Ajeshkumar R. Childhood Bartter’s syndrome: an Indian case series. Indian J Nephrol 2010; 20:207–210.  Back to cited text no. 54
    
55.
Abdel-Al YK, Badawi MH, Yaeesh SA, Habib YQ, al-Khuffash FA, al-Ghanim MM, al-Najidi AK. Bartter’s syndrome in Arabic children: review of 13 cases. Pediatr Int 1999; 41:299–303.  Back to cited text no. 55
    
56.
Dillon MJ, Shah V, Mitchell MD. Bartter’s syndrome10 cases in childhood results of long term indomethacin therapy. Q J Med 1979; 48:429–446.  Back to cited text no. 56
    
57.
Karet E. Monogenic tubular salt and acid transporter disorders. J Nephrol 2005; 15:57–68.  Back to cited text no. 57
    
58.
Shalev H, Ohali M, Kachko L, Landau D. The neonatal variant of Bartter syndrome and deafness: preservation of renal function. Pediatrics 2003; 112:628–633.  Back to cited text no. 58
    
59.
Garel L, Filiatrault D, Robitaille P. Nephrocalcinosis in Bartter’s syndrome. Pediatr Nephrol 1998; 2:315–317.  Back to cited text no. 59
    
60.
Bianchetti MG, Edefonti A, Bettinelli A. The biochemical diagnosis of Gitelman disease and the definition of ‘hypocalciuria’. Pediatr Nephrol 2003; 18:409–411.  Back to cited text no. 60
    
61.
Bhamkar RP, Gajendragadkar A. Antenatal Bartter’s syndrome with sensorineural deafness. Indian J Nephrol 2009; 19:23–26.  Back to cited text no. 61
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62.
Abdulrahman MB, Amirlak I, Ali K et al. Bartter’s syndrome in two Arab infants. Emirates Med J 1992; 10:143–147.  Back to cited text no. 62
    
63.
Kleta R, Basoglu C, Kuwertz-Broking E. New treatment options for Bartter’s syndrome. N Engl J Med 2000; 343:661–662.  Back to cited text no. 63
    
64.
Schachter AD, Arbus GS, Alexander RJ, Balfe JW. Nonsteroidal anti-inflammatory drug-associated nephrotoxicity in Bartter syndrome. Pediatr Nephrol 1998; 12:775–777.  Back to cited text no. 64
    
65.
Pal P. Bartter syndrome. Child Newborn 2007; 11:75–77.  Back to cited text no. 65
    
66.
Konrad M, Vollmer M, Lemmink HH, van den Heuvel LP, Jeck N, Vargas-Poussou R et al. Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome. J Am Soc Nephrol 2000; 11:1449–1459.  Back to cited text no. 66
    


    Figures

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