Saudi Journal of Kidney Diseases and Transplantation

ORIGINAL ARTICLE
Year
: 2013  |  Volume : 24  |  Issue : 2  |  Page : 292--296

Pseudo-bartter syndrome, pattern and correlation with other cystic fibrosis features


Muna M Dahabreh, Abdelhamid S Najada 
 Pediatric Pulmonology Division, Queen Rania Al-Abdullah Hospital for Children, Amman, Jordan

Correspondence Address:
Abdelhamid S Najada
Pediatric Pulmonology Division, Queen Rania Al-Abdullah Hospital for Children, Amman
Jordan

Abstract

Pseudo-Bartter Syndrome (PBS), although quite common in patients with cystic fibrosis (CF), is often missed as simple dehydration or Bartter syndrome. This study was performed in patients with PBS to compare the pattern and course of the disease with those with CF not manifesting with this syndrome. All patients with CF who attended the respiratory clinic at Queen Rania Al-Abdallah Hospital from January 2000 to April 2010 were included in this retrospective case-control study. A specially formulated data sheet was used and those with PBS and those not having the syndrome were identified. A total of 110 patients (51% female) with CF with a median age of seven years were followed-up. Eighteen (16.3%) of them had one or more episodes of PBS. The median follow-up period was 6.2 years. All the episodes occurred during summer and in infancy. Median age of the initial episode of PBS was three months. One-third of them were initially followed at the nephrology clinic. Three patterns of PBS were identified: single episode in three (16.6%) patients, recurrent in 12 (66.6%) patients and chronic in three (16.6%) patients. Early colonization of Pseudomonas spp before 1 st birthday was seen in 44% patients with PBS compared with 12% in other CF patients (P-value = 0.0075). The total number of colonized patients and other CF features at the time of the study did not differ significantly among patients, although the mean Shwachman-Kulczycki score is significantly lower in those with recurrent PBS (69 compared with 85 in other CF patients). Gene mutation was identified in only 30% of the entire cohort. PBS is common in patients with CF, and it should be kept in mind in any patient with hypotonic dehydration and metabolic alkalosis. Recurrent pattern is associated with earlier Pseudomonas colonization.



How to cite this article:
Dahabreh MM, Najada AS. Pseudo-bartter syndrome, pattern and correlation with other cystic fibrosis features.Saudi J Kidney Dis Transpl 2013;24:292-296


How to cite this URL:
Dahabreh MM, Najada AS. Pseudo-bartter syndrome, pattern and correlation with other cystic fibrosis features. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2019 Dec 12 ];24:292-296
Available from: http://www.sjkdt.org/text.asp?2013/24/2/292/109579


Full Text

 Introduction



Pseudo-Bartter Syndrome (PBS) is quite a common manifestation of cystic fibrosis (CF), particularly in countries with a hot climate. [1],[2],[3] It is often missed as either a simple dehydration or is misdiagnosed as Barrter syndrome. It commonly presents as recurrent episodes of dehydration with hypoelctrolemia and metabolic alkaloisis in infancy, particularly in summer. [4] During very hot summer, it might manifest in adult patients with CF. [5] To the best of our knowledge, there are no studies published that looked at the difference in features of CF patients with and without PBS. In this study, we identified patients with PBS and, later, a correlation was performed with the genotype and other features of CF.

 Patients and Methods



All patients with CF and those manifesting PBS who attended the respiratory clinic at Queen Rania Alabdallah Hospital for Children between January 2000 and April 2010 were included in the study. The study design was a retrospective case-control study in which children with CF manifesting PBS were compared with those without PBS. PBS is defined as an episode of dehydration with low sodium (<135 mEq/L), low potassium (<3.5 mEq/L), low chloride (<95 mEq/L) and metabolic alkalosis in patients with CF. A total of 110 children with confirmed CF were included. The diagnosis of CF was made by two sweat chloride readings above 60 mmol/L in two separate occasions in addition to classical clinical manifestations. Patients with CF who underwent abdominal surgery for meconium ileus and manifested hyponatremia were excluded from the PBS group. Careful review of the charts of all patients with or without PBS was conducted. Data collected included age at presentation of first episode of metabolic alkalosis, recurrence, sex, presence of other features of CF (respiratory, gastrointestinal and liver involvement) and results of study of gene mutation. Deep throat or sputum cultures and pulmonary function test, when applicable, were performed monthly on each outpatient clinic. Routine blood tests including liver enzymes were performed six monthly as per the protocol at our institute. Genetic testing was carried out using Innohep Belgium kit for 36 mutations for all CF children and Shwachman-Kulczycki score was performed on all patients at the time of the study.

Ethical approval

The Ethical committee of the Royal Medical Services approved the study.

 Statistical Analysis



The Z-test of the difference between two populations was used to investigate the statistical difference between patients with patients with PBS and those without PBS. P-value was considered significant if it was less than 0.05.

 Results



A total of 18 patients (nine females) with PBS were identified. The median age for all patients at the time of the study was seven years and the median follow-up was for 6.2 years. Median age of first episode of PSB was three months, and all episodes occurred in summer and before the first birthday. Those with PBS constituted 16.3% of all children with CF at our clinic; in 9%, it was the initial manifestation of CF. The youngest patient was one month at the time of the 1 st episode of PBS and the oldest was 12 months. Patients with PBS had earlier diagnosis of cystic fibrosis than other patients with CF (three months compared with one year in other patients) [Table 1]. Thirty-three percent were followed initially in the nephrology clinic as Bartter syndrome. All of them had serum sodium levels less than 132 meq/L during the episode. Fifty-five percent had serum sodium between 132 and 126 mEq/ L. Thirty-three percent had serum sodium between 126 and 120 mEq/L and two (11%) had serum sodium less than 120 mEq/L. Two patients with previous abdominal surgery and hyponatremia in the Intensive Care Unit were excluded from the PBS group because the hyponatremia might be a complication or might be a iatrogenic.{Table 1}

Three patterns of PBS were identified as shown in [Table 2]. The first constituted one single acute episode, corrected by intravenous rehydration, and did not require salt supplement at home. It was seen in three; two of them are siblings (ages seven and three years). Both were homozygous for M2789 + 5G and had no other CF features. The other one, now ten years old, had M.G.85 gene mutation and manifested with only mild pancreatic insufficiency. The second pattern, with recurrent acute episodes, was seen in 12 patients with a total of 40 episodes of dehydrations. Only two of them had CF gene mutations, one with homozygous MN1303k gene mutation and another with MF508del MW 1282. Most of them had respiratory manifestations and pancreatic insufficiency since the first episode of PBS. All the attacks were preceded by exacerbation of cough, followed by poor feeding and hypoactivity. The third pattern with chronic persistent hypoelectrolytemia was seen in three patients; two of them are cousins (eight and 3.8 years old), one had associated non-obstructive left-sided hydronephrosis and had been diagnosed initially as having Bartter syndrome and the other had hypertension with high serum aldosterone and renin levels and was diagnosed initially as Liddle's syndrome. The blood pressure and electrolytes normalized with good proper hydration. Both had homozygous M2789+5G CF gene mutation. They developed respiratory symptoms later in their life after the age of two years and so was referred to the respiratory clinic where the diagnosis of CF was made. Patients with the isolated single episode and those with the recurrent episodes had both clinical and laboratory features of dehydration during the episodes. Those with the chronic pattern, although wasted, were clinically not dehydrated and had mild elevation of blood urea nitrogen at their initial manifestation. Otherwise, there was no difference regarding the degree of hyponatremia, hypochloremia and hypokalemia among the three patterns.{Table 2}

Pseudomonas spp was isolated in eight patients (44.4%) in the study group (seven in recurrent and one in chronic) before their 1 st birthday compared with 12% in others with median age of first isolation was six months compared with 3 years in those without PBS (P <0.05), as shown in [Table 2]. Other clinical features like clubbing, failure to thrive, nasal polyps, liver disease and bronchiectasis did not differ significantly, although Shwachman-Kulczycki score is significantly lower in those with PBS (69 versus 85 in those without PBS).

 Discussion



Our study showed that PBS is quite common in children with CF as an initial presentation and as a complication in Jordan, and found in 16.3% of our cohort. This is nearly similar to what was reported from other countries. PBS was found in 12% of CF patients reported by Yalcin et al from Turkey and in eight patients of 12 patients reported by Al-Mobaireek et al from Saudi Arabia. [1],[2] A study from Spain showed that the occurrence of PBS as a presentation of CF was 16.8%. Age at presentation was between three and 14 months, which is similar to our study group. [3]

We described three patterns of PBS in our cohort [Table 1]. The first pattern was seen as single isolated attack in infancy without other CF manifestations that resolved with proper hydration. Both siblings were homozygous for M2789+5G gene mutation, which is not reported yet to manifest only with PBS in the absence of respiratory and gastro-intestinal manifestations. PBS has been reported as the sole manifestation of CF without other CF features. [5] Most of these mild CF phenotypes are associated with specific mutations, such as T338I, D110E and D110H. [6],[7],[8] Recently, Salvatore et al reported a rare D575G mutation presenting with PBS with pancreatic insufficiency and mild pulmonary involvement in a 10-month-old child from southern Italy. [9]

The recurrent episodic pattern most commonly described in the literature was seen among the majority of our cohort. Interestingly, more than half of our patients had earlier colonization with Pseudomonas than other children with CF, and all of them had respiratory and gastro-intestinal symptoms early on. All infants in these patterns had clinical and laboratory evidence of dehydration, and all the episodes of dehydration were preceded by exacerbation of respiratory symptoms. More than two-thirds of the patients with CF reported by Al-Mobiareek et al were colonized with Pseudomonas spp before their first birthday, and 60% of them manifested PBS. [2] One might speculate that dehydration might cause more viscidity of airway secretions that make it more liable to Pseudomonas colonization. On the other hand, the episodic activation of Pseudomonas infection in the lung might initiate poor feeding, which, in the presence of profuse sweating, might predispose to PBS in susceptible children. Despite earlier Pseudomonas colonization in these patients, the total number of colonized patients and the presence of brochiectasis did not differ significantly from the rest of our patients, although the Miculich score was significantly lower at the time of the study.

The chronic pattern was seen in three patients, and all of them had failure to thrive at initial presentation, although they were not clinically dehydrated. Two of them are cousins carrying the same gene mutation M2789+5G. One had non-obstructive hydronephrosis and the other had initial hypertension. Hydronephrosis is never reported yet in patients with CF, and is thought to be present in conditions associated with polyuria. [10],[11] Renal impairment in CF is usually secondary to drug toxicity. [11] Tsugaya et al reported PBS manifestation in an infant with unilateral multicystic dysplastic kidney and congenital contralateral hydronephrosis, although he did not have CF. [10],[12] In fact, the seven cases reported by Kennedy et al as chronic salt depletion were episodic rather than chronic, and they had recurrent dehydrations. [13]

We speculate that the hypertension in the other child is due to chronic contraction of intravascular volume and secondary hyperaldosteronism and hyperreninemia. The latter are well documented in PBS.

Patients with PBS in our cohort had earlier diagnosis of CF as PBS is more specific to CF than other manifestations. Actually, CF should be considered in the differential diagnosis in any infant with chemical manifestations suggestive of Bartter syndrome. [14] This is most important in countries where neonatal screening test for CF is not available because the disease might be monosymptomatic for several years. In India, they consider patients with diarrhea and metabolic alkalosis as having CF even without performing the sweat chloride test because of non-availability of the latter in some regions. [14] This, we believe, should apply to all developing countries.

Delta F508 gene mutation was seen in only one patient with PBS, and in the heterozygous form, and in four other patients with an overall prevalence of 4% in our cohort with CF. More than half of the patients with PBS reported by Kose et al have F508, which is the most common mutation found in nearly 75% of the patients with CF in a Caucasian population. [5],[14] This means that different populations might have their own specific mutations.

We conclude that PBS should be kept in mind as a quite specific and common manifestation for CF and that recurrent PBS is associated with earlier colonization of Pseudomonas infection. CF genotypes behave differently in different populations.

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