Article

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

Department for Pulmonology and Bronchology, Mother and Child Health Institute of Serbia "Dr Vukan Cupić", Belgrade, Serbia.
Vojnosanitetski pregled. Military-medical and pharmaceutical review (Impact Factor: 0.29). 04/2012; 69(4):367-9.
Source: PubMed
ABSTRACT
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.
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.
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.

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Available from: Radovan Bogdanovic, Jan 22, 2014
Vojnosanit Pregl 2012; 69(4): 367–369. VOJNOSANITETSKI PREGLED Strana 367
Correspondence to: Aleksandar Sovtiý, Department for Pulmonology and Bronchology, Mother and Child Health Institute of Serbia
“Dr Vukan þupiý”, Radoja Dakiýa 6, 11 000 Belgrade, Serbia. Phone/Fax: +381 11 310 8158. E-mail: asovtic@eunet.rs
CASE REPORT
UDC: 616-053.2::616-056.7
DOI: 10.2298/VSP1204367S
Atypical presentation of cystic fibrosis – obese adolescent with
hypertension and pseudo-Bartter’s syndrome
Atipiþna prezentacija cistiþne fibroze – gojazni adolescent sa hipertenzijom i
pseudo-Barterovim sindromom
Aleksandar Sovtiü*, Predrag Miniü*, Radovan Bogdanoviü
, Nataša Stajiü
,
Milan Rodiü*, Gordana Markoviü-Sovtiü*
*Department for Pulmonology and Bronchology,
Department for Nephrology, Mother
and Child Health Institute of Serbia “Dr Vukan ýupiü”, Belgrade, Serbia
Abstract
Introduction. Infants with cystic fibrosis may fail to thrive
despite recommended caloric intake because of electrolyte
disurbances caused by salt depletion resulting in hypochlo-
remic 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 as-
sociated with dehydration and acute renal insufficiency.
Laboratory analysis showed hypochloremic metabolic alka-
losis with hyponatremia and hypokalemia. On admission the
boy was obese, with body weight of 95.5 kg (> P
97
), height
174 cm (> P
75
), and body mass index of 31.2 kg/m
2
(> P
95
).
Physical examination was inconclusive. Blood pressure hol-
ter 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. Conclu-
sion. To our knowledge, this is the first reported case of
atypical presentation of cystic fibrosis in an adolescent pre-
sented with pseudo-Bartter's syndrome and signs of obesity
and hypertension. We suggest that every patient with hypo-
chloremic metabolic alkalosis should be evaluated for cystic
fibrosis.
Key words:
cystic fibrosis; diagnosis; hypertension; obesity;
adolescent.
Apstrakt
Uvod. Odojÿad obolela od cistiÿne fibroze mogu zaostajati u
težini uprkos dobrom kalorijskom unosu, zbog elektrolitnih
poremeýaja prouzrokovanih gubitkom soli, što dovodi do hi-
pohloremijske metaboliÿke alkaloze ili pseudo-Barterovog
sindroma. Simptomi najÿýe poÿinju u uzrastu odojÿeta, ali
mogu biti inicijalna manifestacija oboljenja kod predhodno
zdravih adolescenata. Prikaz bolesnika. Deÿak uzrasta 15
godina primljen je zbog ispitivanja ponavljanih epizoda mala-
ksalosti, udruženih sa dehidracijom i akutnom bubrežnom in-
suficijencijom. Laboratorijskim analizama utvrĀeno je posto-
janje hipohloremijske metaboliÿke alkaloze sa hiponatrijemi-
jom i hipokalijemijom. Deÿak je bio gojazan sa telesnom ma-
som 95,9 kg (> P
97
), telesnom visinom 174 cm (> P
75
) i inde-
ksom telesne mase 31,2 kg/m
2
(> P
95
). Fizikalni nalaz bio je
uredan. Holter monitoringom arterijskog pritiska utvrĀena je
znaÿajna sistolna hipertenzija. Rutinski pregled urina, nivo
proteina i elektrolita u urinu, bili su normalni, kao i koncen-
tracija renina i aldosterona u serumu. Vrednost hlorida u
znoju iznosila je 63 mmol/L. Genetskim probama potvrĀena
je dijagnoza cistiÿne fibroze. Zakljuÿak. Prema saznanjima
autora, ovo je prvi prikaz adolescenta sa atipiÿnom prezetaci-
jom citiÿne fibroze, kod koga se bolest ispoljila kao pseudo-
Barterov sindrom, gojaznost i hipertenzija. Kod svakog bole-
snika kome se utvrdi hipohloremijska metaboliÿka alkaloza
treba razmotriti postojanje cistiÿne fibroze.
Kljuÿne reÿi:
cistiÿna fibroza; dijagnoza; hipertenzija; gojaznost;
adolescenti.
Introduction
Cystic fibrosis (CF) is the most common autosomal re-
cessive 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 fi-
brosis may fail to thrive despite recommended caloric intake
because of electrolyte disturbances caused by salt depletion
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Sovtiý A, et al. Vojnosanit Pregl 2012; 69(4): 367–369.
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 intra-
venous infusion of fluids. These were first observed at the
age of 10, usually occurred during summer and were pro-
voked by physical efforts (sports training) which led to ex-
cessive sweating and malaise that sometimes resolved spon-
taneously. 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 bron-
chodilators for acute respiratory infections associated with
wheezing. Recently he was sometimes complaining on dysp-
nea during exercise, but he had neither chronic sputum pro-
duction nor recurrent pneumonias. He had atopic dermatitis,
and positive family history of atopy. Skin prick tests for in-
halation allergens were negative. He did not have prolonged
neonatal jaundice, meconial ileus, greasy stools or rectal
prolapses. Histories of cyclic vomiting, dyspepsia, abdomi-
nal 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. Spirome-
try, whole body plethysmography and impulse oscilometry
showed normal values. Ergospirometry results were above
normal values for age.
Pharyngeal aspirate was negative for bacterial patho-
gens. Blood gas analysis and oxygen saturation were within
normal range. Routine urinalysis, protein and electrolyte lev-
els in urine were also normal. Plasma renin and aldosteron
were normal. Fecal elastase level was normal. Blood pres-
sure (BP) was elevated and subsequent holter monitoring
proved significant systolic hypertension. Sweat chloride con-
centration 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 bron-
chiectasis in middle and lingular lobes. Abdominal and heart
ultrasound were normal, without portal or pulmonary hyper-
tension. 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 usu-
ally within normal range, with normal sweat chloride level.
Classical form of Bartter’s syndrome is also characterized by
the onset in early childhood
4–6
. 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
1–3
. In one of
the largest cohort presented so far, median age at the pres-
entation was 4 months
2
.
First reported by Wagner et al.
7
, G126D is a non-
common missense mutation located in exon 4 of the CFTR
gene. It was reported in an infant who was compound het-
erozygote for deltaF508 and G126D mutations, and had
pancreatic insufficiency. We report an adolescent patient
with the same genotype, but with mild phenotype and pan-
creatic sufficiency, who presented an unusual association
of obesity and hypertension with pseudo-Bartter’s syn-
drome.
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 pa-
tient. 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 hypo-
chloremic metabolic alkalosis should be evaluated for CF.
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Received on March 28, 2011.
Revised on August 16, 2011.
Accepted on September 5, 2011.
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  • [Show abstract] [Hide abstract] ABSTRACT: Cystic fibrosis per se can sometimes lead to hyponatremia, hypokalemia, hypochloremia or hyperbicarbonatemia. This tendency was first documented 60 years ago and has subsequently been confirmed in single case reports or small case series, most of which were retrospective. However, this issue has not been addressed analytically. We have therefore systematically reviewed and analyzed the available literature on this subject. This was a systematic review of the literature. The reports included in this review cover 172 subacute and 90 chronic cases of electrolyte imbalances in patients with cystic fibrosis. The male:female ratio was 1.57. Electrolyte abnormalities were mostly associated with clinically inapparent fluid volume depletion, mainly affected patients aged ≤2.5 years, frequently tended to recur and often were found before the diagnosis of cystic fibrosis was established. Subacute presentation often included an history of heat exposure, vomiting, excessive sweating and pulmonary infection. History of chronic presentation, in contrast, was often inconspicuous. The tendency to hypochloremia, hypokalemia and metabolic alkalosis was similar between subacute and chronic patients, with hyponatremia being more pronounced (P < 0.02) in subacute compared to chronic presentations. Subacute cases were treated parenterally; chronic ones were usually managed with oral salt supplementation. Retention of urea and creatinine was documented in 38 % of subacute cases. The findings of our review suggest that physicians should be aware that electrolyte abnormalities can occur both as a presenting and a recurring feature of cystic fibrosis.
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