املجلة الصحية لرشق املتوسط املجلد السادس عرش العدد السادس

Case report Pseudo-Bartter as an initial presentation of . A case report and review of the literature M.A. Marah1

Introduction chloride 84 mmol/L, bicarbonate 29 Further evaluation, around the age mmol/L and creatinine 0.4 mg/dL. He of 1 year and while he was clinically Cystic fibrosis (CF) is an autosomal required intravenous fluid therapy and stable, revealed a thriving child with recessive condition caused by the was discharged after correction of his the following serum biochemical re- mutation of the cystic fibrosis trans- biochemical abnormalities. sults: sodium 133 mmol/L, potassium membrane regulator gene (CFTR) on He was readmitted 5 more times 3.4 mmol/L, chloride 100 mmol/L and bicarbonate 22 mmol/L. The serum chromosome 7. Although it primarily over a 2-year period with episodes of affects the respiratory and gastrointes- levels of (99 ng/dL) and diarrhoea and vomiting associated tinal tracts, it can also involve other (84 ng/dL) were normal, so was with similar biochemical abnormalities organs. It may also cause electrolyte and urinary chloride excretion (20 mg/dL) (Table 1). He never had significant acid base disturbances, rarely the mode but the fractional excretion of potas- of presentation. This can result in dif- respiratory problems throughout that sium was elevated at 67%. Hyponatrae- ficulty in making an early diagnosis period, The possibility of Bartter syn- mia was interpreted as being secondary in the absence of other characteristic drome was raised, but the diagnosis to prolonged diarrhoea and vomiting, clinical features. was dismissed as his blood pressure was hypokalaemia to stool losses, metabolic We report here such a case which initially high, urinary chloride excretion to extra cellular compartment presented in infancy. was low with only slightly elevated levels contraction and the initial but transient of serum renin (320 ng/dL at rest and rise in blood pressure to secondary standing) and aldosterone (195 ng/dL . Case report at rest and 206 ng/dL while standing). was excluded in view of the absence A 6-month old Yemeni infant presented with an 8-day history of diarrhoea and Table 1 Biochemical results of the patient at various admissions vomiting. He was born at full term with Biochemical measure Date an uneventful prenatal, perinatal and 24/4/99 09/5/99 25/9/99 04/7/99 03/9/01 postnatal history. His parents, who are Plasma Na (mEq/L) 117 131 125 127 126 first-degree cousins, and his 4-year-old Plasma Cl (mEq/L) 84 88 85 82 89 sister were healthy. Serum K (mEq/L) 3.1 3 4 3.2 2.7 On presentation, he was febrile and Plasma HCO3 (mEq/L) 30 28 28 28 29 had moderate dehydration (< 10%). His Blood Urea (mg/dL) 8 6 25 34 23 weight was 7.8 kg (just above the 5th Serum Creatinine (mg/dL) – 0.4 0.6 0.7 0.9 percentile), length 69 cm (on the 10th Plasma pH 7.54 – 7.5 7.55 7.56 percentile) and head circumference 43.8 HCO 31 – 29 30.3 31 cm (on the 5th percentile). His blood 3 Base excess 4 – 2 4 5 pressure fluctuated between 70/50 mmHg and 100/80 mmHg. The rest of Urinary Na (mEq/L) – 10 <10 – < 10 his examination was unremarkable. Urinary K (mEq/L) – 43 – – 54.7 Urinary Cl (mEq/L) – <10 <10 – < 10 Analysis of serum electrolytes gave the following results: sodium Serum aldosterone (ng/dL) 99.2 – – – – 124 mmol/L, potassium 4 mmol/L, Serum renin (ng/dL) 84 – – – –

1Paediatric Department, Al Ain Hospital, Al Ain, United Arab Emirates (Correspondence to M.A. Marah: [email protected]). Received: 10/06/08; accepted: 20/07/08

699 EMHJ • Vol. 16 No. 6 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale

of , hypocalcaemia, Discussion massive sodium chloride loss which re- hypomagnesaemia, hypermagnesuria sults in significant extracellular volume or significant hypokalaemia. The patient CF is an inherited disorder affecting contraction and secondary hyperaldos- was discharged on sodium chloride and most organ,s especially the exocrine teronism. This hyperaldosteronism will potassium chloride supplementation. glands. It is associated with a large lead to increased potassium losses both After being lost to follow-up for number of mutations affecting the in the sweat and the urine, resulting in several years, he was seen again at the , the commonest being hypokalaemia [3,8–14]. age of 8 years when he presented with mutation of the delta F508 on chromo- The pathophysiology of metabolic sever gastroenteritis, hypovolaemic some 7. The manifestation of the disease alkalosis includes: volume depletion shock and chest infection. His height can appear at birth or later in the life ac- leading to a relatively high bicarbonate and weight were below the 3rd percen- cording to the type of mutation, which level in the contracted extracellular vol- also predicts the severity of the disease tile, temperature was 38.7 °C, heart rate ume (haemoconcentration) [3,8,9,15], [1]. The most common systems affect- and low extracellular chloride leading to 98/min, respiratory rate 30/min, blood ed are respiratory (where the typical increased reabsorption of bicarbonate pressure 70/50 mmHg, O saturation 2 presentation includes recurrent pneu- to replace the lost extracellular anions 88% in room air and capillary refill monia and obstructive lung disease) (chloride and bicarbonate) [3,9]. In 4 seconds. He had marked finger and and digestive (secondary to pancreatic addition, the extracellular volume toe clubbing, with bilateral crepitations insufficiency) leading to growth failure depletion leads to decreased filtered heard on auscultation. [1]. Other manifestations include renal load of bicarbonate in the urine due to He underwent fluid resuscita- agenesis [2] and absence of vas deferens decreased Glomerular filtration rate tion and investigations showed the [1,2]. Uncommonly, it can present as (GFR) [3,8] and the hypokalaemia following results: serum sodium an acid-base and electrolyte imbalance, itself can maintain and generate meta- 128 mmol/L, chloride 76 mmol/L, such as hypokalaemia, hyponatraemia bolic alkalosis [3,8,15,16]. The effect of potassium 3.3 mmol/L, bicarbonate and . these electrolyte losses is the activation 28 mmol/L, anion gap 15.6 mmol/L, Most children with CF presenting of the renin–angiotensin system and urea 35 mg/dL, creatinine 1.3 mg/ as hypoelectrolytaemia and metabolic stimulation of sodium cation (hydro- dL, calcium 10.5 mg/dL, phosphorus alkalosis (so-called pseudo-Bartter) gen, potassium) exchange, with result- 7.6mg/dL and magnesium 2.3 mg/ were under the age of 6 months [3,4]. ing alkalosis and potassium depletion. dL. Blood gas results were: pH 7.51, Multiple inter-related factors have been Although hyperaldosteronism without pCO2 48.4 mmHg, pO2 65 mmHg, incriminated in its pathophysiology. distal sodium delivery will not cause al- base excess 6.1 mmol/L, bicarbonate Normally, with the cystic fibrosis trans- kalosis, an increase in mineralocorticoid 31.6 mmol/L. Urinary electrolytes membrane regulator (CFTR) gene with distal proton delivery would, as in results were: sodium < 10 mmol/L, regulating sweat production, normal the case of Bartter syndrome and chron- chloride < 15 mmol/L, potassium 117 sweat glands produce iso-osmotic pri- ic use. Studies have shown that mmol/L, calcium excretion < 2 mg/ mary sweat, partly by chloride secre- some changes in renal sodium handling day and magnesium excretion 2.3 mg/ tion across the apical CFTR [5]. The [17] and free water clearance [18] oc- curs in CF patients. Furthermore, the day. Bilateral streaky infiltrates were water-impermeable sweat duct reab- CFTR (or CFTR-like) gene or protein seen on chest radiography. Sputum sorbs sodium chloride transcellularly, has been located in the proximal tubules culture grew Pseudomonas aeruginosa leading to the excretion of hypotonic sweat, enabling the body to regulate its of rabbits [19,20], rats [21], mice [20] and blood and urine cultures revealed temperature with minimal loss of elec- and also in human distal tubules [22]. no bacterial growth. Fluid therapy led trolytes [5]. The volume of sweat in CF Thus, a volume-depleted CF patient can to gradual biochemical correction over patient is different from that in healthy still maintain distal sodium delivery due 3 days. people [6]. Although the production of to dysfunctional CFTR. The suspected diagnosis of cystic primary sweat is relatively normal in CF Gastrointestinal losses act as con- fibrosis was confirmed with a sweat patients [5], the dysfunctional CFTR tributory factors, accentuating an un- chloride level of 120 mmol/L and in the sweat duct results in excessive derlying salt depletion and metabolic homo­zygozity for the Delta F 508 gene sodium and chloride loss in the final alkalosis. In all CF infants with acute or on genetic studies. The child was started sweat [5,6]. This loss in sodium chloride chronic fluid and electrolyte losses with on standard CF therapy. He is currently is more marked in hot weather where sweating, their metabolic abnormali- doing well regarding weight gain and his the rate of sweat production may reach ties and condition are aggravated by blood chemistry remains normal. up to 2 litres/hour [5–7], leading to acute intercurrent episodes of vomiting,

700 املجلة الصحية لرشق املتوسط املجلد السادس عرش العدد السادس

diarrhoea, or respiratory symptoms and decrease in filter load of bicarbo- stenosis), congenital chloride-losing di- [3,7,10]. These intercurrent illness acts nate secondary to decreased GFR. This arrhoea, Gittelman syndrome, diuretic as a precipitating event aggravating the volume depletion led to activation of the use and primary hyperaldosteronism underlying metabolic alkalosis and hy- renin–angiotensin system and second- [1,3,8,10,15]. A practical approach to poelectrolytaemia. In addition, infants ary hyperaldosteronism (Table 1) with deal with hypochloraemic metabolic with CF are prone to develop episodes enhanced urinary and sweat potassium alkalosis is suggested. First, urinary chlo- of hyponatraemic hypochloraemic de- excretion. This resulted in hypokalae- ride level should be measured: if very hydration with metabolic alkalosis, due mia, which by itself could aggravate and high, Bartter syndrome is very likely. to excess salt loss with sweating, espe- maintain the metabolic alkalosis. If it is not elevated, other non-urinary cially in regions with a hot, dry climate, Hypochloraemic metabolic alka- chloride losses, such as stool losses during the warmer months [3,7,10]. losis with increased serum aldosterone (congenital chloride diarrhoea or laxa- Breastfed infants are more prone to have and renin levels occurs in both Bartter tive abuse) or excessive losses in sweat such electrolyte derangement especially and in CF (pseudo-Bartter) 12,13,15[ ] (CF) should be considered. in hot weather due to low salt content in syndrome. The main difference is that the breast milk [10]. urinary chloride losses in Bartter syn- In our patient, the volume depletion drome are high, while they are low in CF Conclusion was most likely secondary to many fac- (with elevated sweat chloride losses). tors including: hot climate, episodes of When faced with a child with hy- When confronted with hypochlorae- gastroenteritis, recurrent vomiting and pochloraemic hypokalaemic metabolic mic hypokalaemic metabolic alkalosis, intercurrent infections. It led to contrac- alkalosis, causes other than Bartter syn- the possibility of CF must always be tion alkalosis due to the relative increase drome need also to be considered. They considered, even in the absence of char- in serum bicarbonate concentration include persistent vomiting (as in pyloric acteristics clinical features.

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