Article Type : Case Report
Authors : Kamal El Bakry A, Singh B and Devadas N
Keywords : Neonatal; Bartter syndrome
We report a case of Neonatal Bartter syndrome in a baby girl born at 25 weeks+ 5 days of gestational age to a Primi mother with antenatal polyhydramnios. Baby was admitted as a case of respiratory distress syndrome in NICU and she developed severe dehydration leading to pre-renal renal impairment along with typical biochemical changes of hypokalaemic, hypochloraemic metabolic alkalosis.
Bartter syndrome is a rare condition due to defective absorption of sodium and chloride in the Thick ascending loop of Henle resulting in excessive loss of urinary electrolytes and fluid. High index of suspicion is necessary to diagnose the case as biochemical changes which are characteristic of the condition such as hypokalaemic hypochloraemic metabolic alkalosis may be masked early in neonatal period especially with polyuria and dehydration.
Case Report
This extreme preterm female baby born at 25 weeks and
5 days gestational age to a Primi mother (birth weight of 700 grams) was admitted
to our Neonatal unit as a case of respiratory distress syndrome. Mother had
severe polyhydramnios. Amnio reduction was done in the antenatal period and
amniotic fluid was sent for analysis which was unremarkable. Baby was managed
with surfactant administration and respiratory support with nasal CPAP and she
remained stable till 2nd week of life when Fio2 requirement gradually started
to increase. Echocardiography revealed large PDA which was ligated on 21 st day
of life and again baby was stable on nasal CPAP.
In the second week of life baby had raised urea and
creatinine levels highest urea being 35.5mmol/L and highest value of creatinine
294 mmol/L on 9th day of life. Since then her urea levels have decreased upto
10 mmol/l at the end of 2 weeks and creatinine upto 94 mmol/l by 3rd week of
life. At around 3 weeks of age she developed significant hyponatremia (Na125),
Hypokalemia (K 2.58) and hypochloremia (Cl 71.8). She was also noted to have
compensated metabolic alkalosis and was failing to thrive. Blood gas (pH 7.53,
pCO2 82.2, BE 37.9, HCO3 68.2).Low serum potassium and chloride levels were
persistent even after large amounts of supplements.
Neonatal Bartter's syndrome was suspected. Her urine
output has always been more >6 ml/kg/hour. Her urine chloride levels were
found to be high. (103 mmol/l), Urine calcium creatinine ratio 1.15 (mg/dl),
random urine sodium (105 mmol/l), urine potassium (13mmol/l). Her electrolyte
imbalance was corrected by Intravenous supplements and TPN and later commenced
on oral supplements of sodium and potassium chloride. She required large
amounts of oral potassium chloride and sodium chloride to maintain the
electrolyte levels within normal range.
She continued to have significant metabolic alkalosis
and most of the time it was compensated. Her renal function tests improved
gradually with decline of creatinine and urea. Her electrolyte disturbances
were managed with adjustment of electrolyte supplements. She also developed
hypocalcemia (serum ionized calcium varying from 0.8 -1.10 mmol/l) and put on
oral calcium supplements. Her Magnesium levels have always been in normal
range. Baby developed chronic lung disease and was oxygen dependent even at the
time of discharge. Repeat ECHO done at three and half months of age revealed
severe Hypertrophic Obstructive Cardiomyopathy (HOCM) along with cleft anterior
mitral leaflet and baby was put on propranolol as advised by pediatric
cardiologist.
USG abdomen revealed bilateral enlarged kidneys with
increased cortical echoes and partially maintained corticomedullary
differentiation. No evidence of nephrocalcinosis.
Baby was discharged at around 6 months of age with
weight of 3.52 Kg (0.4-2nd centile). Head circumference 34 cm (below 0.4
centile) on 28% oxygen by nasal cannula to long term care on oral supplements
of sodium chloride, potassium chloride, multivitamins, ferrous sulfate, oral
calcium and propranolol.
Discussion
Bartter syndrome also called salt-losing tubulopathy
with secondary hyperaldosteronism, originally described by Bartter and
colleagues in 1962 represents a set of closely related, autosomal recessive
renal tubular disorders characterized by hypokalemia, hypochloremia, metabolic
alkalosis, and hyperreninemia with normal blood pressure. Long term activation
of the renin-angiotensin-aldosterone system (RAAS) and subsequent secondary
hyperaldosteronism causes hyperplasia of the juxtaglomerular apparatus and
hence increased renin levels.
The defective sodium chloride transport in the loop of
Henle associated with Bartter syndrome leads to the impaired electrochemical
gradient, which is necessary for calcium and magnesium reabsorption, leading to
increased urinary loss of calcium and magnesium. Nephrocalcinosis is commonly
seen in patients with Bartter syndrome.
Traditionally it had been classified into three main
clinical variants:
· Neonatal (or antenatal) Bartter syndrome
· Classic Bartter syndrome
· Gitelman syndrome
With the advances in molecular
diagnostics it had been found that Bartter syndrome results from mutations in
genes that affect the function of ion channels and transporters that mediate
salt reabsorption in the distal nephron segments. This revelation created a new
classification system for Bartter syndrome on the basis of the underlying
genetics.
Neonatal Bartter syndrome type 1
results from mutations of the gene located on chromosome 15q15-q21 which codes
for Na-K-2Cl co-transporter (NKCC2) of the Thick Ascending Loop of Henle.
Mutations of ROMK gene situated upon chromosome 11q24-25 which codes for K+
channels responsible for recycling and reabsorbing K+ back into tubular lumen
results in Neonatal Bartter type 2.
Neonatal Bartter syndrome may present
as maternal polyhydramnios, secondary to fetal polyuria evident by 24-30 weeks'
gestation. Delivery often occurs before term. The subsequent course is
characterized by life-threatening episodes of fluid loss, clinical volume depletion,
and failure to thrive. Some patients with neonatal Bartter syndrome (types IV
and V) develop sensorineural deafness.
Bartter syndrome is diagnosed on the
basis of clinical presentation and laboratory findings, including severe
hypokalemia and metabolic alkalosis in almost all cases. Other abnormalities
include increased serum renin and aldosterone levels along with hypercalciuria.
Urine electrolytes show elevated chloride, sodium, potassium, and PGE2
excretion. Differential diagnoses may include Gitelman’s syndrome, Primary
hyperaldosteronism and Pseudo-Bartter syndrome which were excluded in our case.
While managing the babies with Bartter
syndrome the target is to prevent dehydration and normalize potassium levels in
serum which can be achieved with high doses of oral potassium supplementation. Sodium
supplementation may also be required either by saline infusion in neonatal
period or oral sodium chloride. Indomethacin, a prostaglandin inhibitor has
also been found to be effective in many cases. Bartter syndrome is not curable,
the degree of disability depends on the severity of the receptor dysfunction. With
close monitoring of electrolyte balance, volume status and nutrition long term
prognosis is good.
Finding of hypertrophic obstructive
cardiomyopathy in our case posed a diagnostic dilemma whether it is a separate
entity from Bartter or same genetic mutation is the underlying cause of both
the conditions.