Atypical presentation of cystic fibrosis – obese adolescent with hypertension and pseudo-Bartter ’ s syndrome

Introduction. Infants with cystic fibrosis may fail to thrive despite recommended caloric intake because of electrolyte disurbances caused by salt depletion resulting in hypochloremic metabolic alkalosis or pseudo-Bartter's syndrome. In most patients reported symptoms began in infancy, but it may be an initial presentation of disease in a previously healthy adolescent. Case report. A 15-year-old boy was admitted for evaluation of recurrent episodes of malaise associated with dehydration and acute renal insufficiency. Laboratory analysis showed hypochloremic metabolic alkalosis with hyponatremia and hypokalemia. On admission the boy was obese, with body weight of 95.5 kg (> P97), height 174 cm (> P75), and body mass index of 31.2 kg/m2 (> P95). Physical examination was inconclusive. Blood pressure holter monitoring proved significant systolic hypertension. Routine urinalysis, protein and electrolyte levels in urine were normal. Plasma renin and aldosteron were normal. Sweat chloride concentration was 63 mmol/L. Genetic testing confirmed the diagnosis of cystic fibrosis. Conclusion. To our knowledge, this is the first reported case of atypical presentation of cystic fibrosis in an adolescent presented with pseudo-Bartter's syndrome and signs of obesity and hypertension. We suggest that every patient with hypochloremic metabolic alkalosis should be evaluated for cystic fibrosis.


Introduction
Cystic fibrosis (CF) is the most common autosomal recessive inherited disease in Caucasian's.From their early age patients mostly develop symptoms such as malnutrition (due to pancreatic insufficiency) and chronic suppurative lung disease.Very few patients may have mild and atypical CF phenotype.It is also well known that infants with cystic fibrosis may fail to thrive despite recommended caloric intake because of electrolyte disturbances caused by salt depletion resulting in hypochloremic metabolic alkalosis or pseudo-Bartter's syndrome 1 .In most patients reported symptoms began in infancy and mostly resolved with appropriate salt intake at the age of four 1,2 .Nevertheless, it may be an initial presentation of disease in a previously healthy adolescent 3 .

Case report
A 15-year-old boy was admitted for further evaluation of recurrent episodes of malaise associated with dehydration and acute renal insufficiency, requiring correction by intravenous infusion of fluids.These were first observed at the age of 10, usually occurred during summer and were provoked by physical efforts (sports training) which led to excessive sweating and malaise that sometimes resolved spontaneously.The boy was hospitalized twice in local hospital, for more severe symptoms when laboratory analysis showed hypochloremic metabolic alkalosis with hyponatremia and hypokalemia.
He was born on term and was thriving normally.From the age of 4 months, he was periodically treated with bronchodilators for acute respiratory infections associated with wheezing.Recently he was sometimes complaining on dyspnea during exercise, but he had neither chronic sputum production nor recurrent pneumonias.He had atopic dermatitis, and positive family history of atopy.Skin prick tests for inhalation allergens were negative.He did not have prolonged neonatal jaundice, meconial ileus, greasy stools or rectal prolapses.Histories of cyclic vomiting, dyspepsia, abdominal pain or dysuria were all negative.
On admission the boy was obese, with body weight of 95.5 kg ( P 97 ), height 174 cm ( P 75 ), body mass index of 31.2 kg/m 2 ( P 95 ).Auscultatory findings over the chest were normal.The rest physical examination was inconclusive.
Chest radiography showed no abnormalities.Spirometry, whole body plethysmography and impulse oscilometry showed normal values.Ergospirometry results were above normal values for age.
Pharyngeal aspirate was negative for bacterial pathogens.Blood gas analysis and oxygen saturation were within normal range.Routine urinalysis, protein and electrolyte levels in urine were also normal.Plasma renin and aldosteron were normal.Fecal elastase level was normal.Blood pressure (BP) was elevated and subsequent holter monitoring proved significant systolic hypertension.Sweat chloride concentration was elevated -63 mmol/L.
The patient was then referred for genetic testing, which confirmed deltaF508 in one allele, but none of 29 most common mutations in our population was found on another.Therefore, a systematic scan of the whole coding regions of the CF transmembrane conductance regulator (CFTR) gene was performed, which showed that he was compound het-erozygote for deltaF508 and G126D mutations.This result confirmed diagnosis of CF.
Further analyses were done.High resolution computed tomography of the chest showed very mild cylindric bronchiectasis in middle and lingular lobes.Abdominal and heart ultrasound were normal, without portal or pulmonary hypertension.Ultrasound examination of testicles showed several small cysts in the head of the both epididymis which was not uncommon finding in male CF patients.

Discussion
In classical form of Bartter's syndrome renal tubules are unable to reabsorb electrolytes, which lead to its high urine concentrations.In its several subtypes, plasma renin and aldosteron levels are elevated and blood pressure is usually within normal range, with normal sweat chloride level.Classical form of Bartter's syndrome is also characterized by the onset in early childhood [4][5][6] .The findings in our patient, such as late onset of symptoms, hypertension, normal renin and aldosteron levels are not indicative for classical form of Bartter's syndrome.Hypertension found in our patient is probably caused by obesity.
Pseudo-Bartter's syndrome is a metabolic disorder that can be caused by CF, but also by uncontrolled diuretic and laxative use, rigorous chloride-deficient diet, cyclic vomiting and bulimia.Symptoms may include polyuria, polydipsia, vomiting, frequent dehydration and salt craving [1][2][3] .In one of the largest cohort presented so far, median age at the presentation was 4 months 2 .
First reported by Wagner et al. 7 , G126D is a noncommon missense mutation located in exon 4 of the CFTR gene.It was reported in an infant who was compound heterozygote for deltaF508 and G126D mutations, and had pancreatic insufficiency.We report an adolescent patient with the same genotype, but with mild phenotype and pancreatic sufficiency, who presented an unusual association of obesity and hypertension with pseudo-Bartter's syndrome.
It is shown that a long-term survival in CF is probably not caused by residual CFTR function, and that it is possible even with "severe" mutations, like the one found in our patient.It is proposed that mechanisms of a long-term survival include genetic modifiers and environmental factors 8,9 .

Conclusion
As to authors' knowledge, this is the first reported case of atypical presentation of CF in an adolescent presented with pseudo-Bartter's syndrome and clinical signs of obesity and hypertension.We suggest that every patient with hypochloremic metabolic alkalosis should be evaluated for CF.