Pseudo-Bartter’s syndrome revealing cystic fibrosis in an infant caused by
3849 + 1G>A and 4382delA compound heterozygosity
El-Rifai Nahida (firstname.lastname@example.org)1, Hourani Mohammed, Lalau Guy2
1.Department of Pediatrics, Makassed General Hospital, Beirut, Lebanon
2.Biology and Pathology Center, Biochemistry and Molecular Biology Pole, CHRU Lille, France
Cystic fibrosis, Pseudo-Bartter’s syndrome
E-R Nahida, M.D., Department of Pediatrics,
Makassed General Hospital, Riad El_Solh street;
P.O.Box 6301, Beirut 1107 2210, Lebanon.
Tel: +9613082988 |
Fax: +9611646589 |
18 March 2011; accepted 25 March 2011.
Pseudo-Bartter’s (PB) syndrome characterized by hypokalemic metabolic alkalosis and per-
sistent failure to thrive constitutes a rare typical presentation of cystic fibrosis (CF) with prev-
alence of 16.8%. We present a case of CF presenting with failure to thrive, dehydration, PB
syndrome associated with chest infection and primo-colonization with Pseudomonas aeru-
ginosa. Sweat chloride test was 102 mmol⁄L. DNA analysis identified 2 mutations
3849 + 1G>A (intron 19) and 4382delA (exon 24) present in heterozygous status. To the
best of our knowledge, our case is the first reported case in the literature of CF manifested
by PB syndrome associated with chest infection and primo-colonization with Pseudomonas
The genotype 3849 + 1G>A⁄4382delA found in our patient is
described for the first time in the literature. It explains the lung involvement with the dehy-
dration and electrolyte disturbances. The role of the mutation in exon 24 in cases of CF with
PB syndrome remains to be determined.
Cystic fibrosis (CF) is characterized by the dysfunction of
exocrine glands throughout the body including sweat
glands, the pancreas and mucus glands of the respiratory,
gastrointestinal and reproductive tracts. The major clinical
characteristics of CF are pancreatic insufficiency and pro-
gressive lung disease, caused by thick and dehydrated air-
way mucus frequently infected with Pseudomonas and
Staphylococcus, leading to respiratory failure and CF mor-
tality (1). In infancy, it presents typically with combination
of failure to thrive and steatorrhea and respiratory symp-
toms (2). Less frequently, it can present as an acid–base and
electrolyte imbalance such as hyponatremia, hypokalemia,
and metabolic alkalosis or so-called Pseudo-Bartter’s syn-
drome (PB) (1,3–11).
We present a case of CF presenting with failure to thrive,
dehydration, PB syndrome associated with chest infection
and primo-colonization with Pseudomonas aeruginosa.
A 75-day-old girl was born by normal vaginal delivery to a
G2P2A0 mother known to have protein S deficiency. The
baby passed meconium at day 1 of life and discharged home
on the second day. Birth weight was 3 kgs, and height was
49 cm. The baby was exclusively breast-fed and was gaining
weight adequately until 1 month prior to presentation. Arti-
ficial formula was added at that time to breast feeding with
little improvement in weight gain. Two weeks prior to pre-
sentation, the patient started to have productive cough and
decreased appetite associated with hypoactivity for which
she received oral antibiotics. Moreover, she developed
abdominal distension with straining upon defecation for
which she underwent barium enema and was normal. After
that, the patient’s condition deteriorates; she became hypo-
active with total loss of appetite for which she was admitted
to our hospital. Upon admission, the patient was afebrile
and moderately dehydrated. Her weight was 5440 g (50th
percentile), height 57 cm (75th percentile) and head cir-
cumference 40 cm (50th percentile). Vital signs were as
following: respiratory rate was 40⁄mn, pulse rate was 163
and oxygen saturation on room air was 94%. Diffuse rhon-
chi were noticed on chest auscultation with gaseous disten-
sion of the abdomen. The rest of her examination was
After admission, the haemogram was unremarkable. The
108 mmol⁄L (normalrange
2.5 mmol⁄L (normal range 3.5–5.4), chloride 52 mmol⁄L
(normal range 93–110) and bicarbonate 39 mmol⁄L (nor-
mal range 18–22 mmol⁄L). Blood glucose level was fluctu-
ating between 160 and 200 mg⁄dL (normal range 70–110).
Arterial blood gases showed a pH of 7.57, pCO2 of
39 mmHg and pO2 of 71 mmHg. Blood urea nitrogen,
CF, Cystic fibrosis; PB, Pseudo-Bartter’s syndrome.
Acta Pædiatrica ISSN 0803–5253
ª2011 The Author(s)/Acta Pædiatrica ª2011 Foundation Acta Pædiatrica
creatinine and liver function tests were normal. Spot urine
sodium was 15 mmol⁄L, potassium 5.1 mmol⁄L and chlo-
ride 22 mmol⁄L.
Intravenous fluid resuscitation was started with progres-
sive correction of the profound hyponatremia i.e. not
exceeding 12 mmol⁄L per day in addition to the correction
of hypokalemia. Few hours after admission, the patient
respiratory status deteriorates: she became more tachypneic
and developed frequent desaturations. Auscultatory find-
ings included prolonged expiration and inspiratory crackles.
Chest radiograph showed right upper lobe pneumonia.
Deep tracheal aspirate culture taken the day of admission
showed heavy growth of Pseudomonas aeruginosa. Patient
was started on intravenous cefotaxime. Fluid therapy led to
gradual biochemical correction over 4 days. Blood glucose
level normalized as well.
The suspected diagnosis of CF was confirmed with a
sweat chloride of 102 mmol⁄L. (Sweat testing was carried
out after the correction of hydration status and electrolytes
abnormalities.) DNA analysis identified two mutations
3849 + 1G>A (intron 19) and 4382delA (exon 24) present
in heterozygous status.
Following the introduction of 3 mmol⁄kg⁄day of sodium
supplements and supportive treatment of CF, the patient’s
weight improved gradually.
Isolated hyponatremic dehydration or associated with
hypokalemia and metabolic alkalosis as a presentation of
CF has been reported in the literature (4–9). PB syndrome
characterized by hypokalemic metabolic alkalosis and per-
sistent failure to thrive constitutes a rare typical presenta-
tion of the disease with estimated prevalence of 16.8% (5).
In the literature, most children with CF presenting with PB
syndrome were under the age of 6 months (1,3,10,11).
Vomiting and loss of appetite are important warning signs
of possible PB in patients with CF (12).
Several mutations of the CFTR gene associated with hyp-
reported in the literature such as F311L, D110E, D110H,
T3381, N1303K, 2789 + 5G-A, S13F and 3849 + 40 A⁄G
(4,7–11,13). However, none of reported cases have had
respiratory involvement upon diagnosis, and to the best of
our knowledge, our case is the first reported case in the liter-
ature of CF manifested by PB syndrome associated with
chest infection and primo-colonization with Pseudomonas
Our patient had a compound heterozygosity for two
mutations, 3849 + 1G>A on intron 19 and 4382delA on
exon 24, in whom the disease was manifested by PB with
lung involvement. The mutation 3849 + 1G>A in combina-
tion with DF508 was described in the CF mutation database
in a patient with pancreatic insufficiency, and it carries a
severe deleterious effect. Mutations located in exon 24 are
associated with mild form of CF. The respiratory symptoms
appear lately, and lung involvement remains less important
To our knowledge, the genotype 3849 + 1G>A⁄4382delA
found in our patient is described for the first time in the lit-
erature. It explains the lung involvement in combination
with the dehydration and electrolyte disturbances found in
our patient. The role of the mutation in exon 24 in cases of
CF with PB syndrome remains to be determined.
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Pseudo-bartter’s syndrome revealing cystic fibrosis in an infant
Nahida et al.
ª2011 The Author(s)/Acta Pædiatrica ª2011 Foundation Acta Pædiatrica