Antenatal Bartter Syndrome

Antenatal Bartter syndrome is characterized by severe polyhydramnios in mother leading to premature delivery. Antenatal treatment has proven effective to prevent these problems. Postnatally newborns suffer from recurrent episodes of severe dehydration and electrolyte imbalance which can lead to fatal outcome. These manifestations are likely to be overlooked and missed under the umbrella of diagnosis of prematurity. This premature newborn with antenatal polyhydramnios had severe manifestations of polyuria, recurrent dehydration, electrolyte derangements and metabolic alkalosis. She was managed accordingly but unfortunately could not survive beyond 4 weeks.


INTRODUCTION
Bartter syndrome is a rare autosomal recessive renal tubular disorder having two characteristic presentations -Antenatal Bartter Syndrome (ABS) and classic Bartter syndrome.Primary pathology lies in thick ascending loop of Henle (TALH) where there is defective transepithelial reabsorption of chloride.This results in malreabsorption of Na + , K + , Cl -and Ca ++ in TALH and delivery of large volume of urine with high content of Na + , K + , Cl -and Ca ++ to the distal tubule. 1 The disease is characterized by hypokalemia, hyponatremia, hypochloremic metabolic alkalosis, and urinary loss of Na + , K + , Cl -and Ca ++ .Aldosterone, rennin and prostaglandin levels are also high as a secondary phenomenon.
Typical clinical features are fetal polyuria, severe polyhydramnios, intra uterine growth retardation, preterm delivery, postnatal polyuria, episodes of dehydration, recurrent vomiting and failure to thrive.Later in life, they develop nephrocalcinosis due to massive hypercalciuria and frequent fractures due to osteopenia. 2 Various case series and review articles emphasize that babies havig clinical manifestations in neonatal period have more severe presentation. 3,4ence, they need timely recognition and agressive management of dehydration and electrolyte derangements.
This case is being reported for alerting the obstetricians and paediatricians to the presence of severity of clinical manifestations and management issues in neonatal period.

CASE REPORT
A female baby was born to consanguineous parents by LSCS prematurely at 30 weeks gestation due to severe polyhydramnios at Quaid-e-Azam International Hospital, Islamabad.There was history of one intrauterine death at about 30 weeks gestation due to severe polyhydramnios in previous pregnancy.Baby weighed 1.4 kg and was admitted in NICU due to prematurity.She was stabilized with routine care and did not develop respiratory distress or any other expected complications of prematurity.She passed meconium normally but was unable to suck the feeds.So she was maintained on intravenous (I.V.) fluids and nasogastric (NG) feeding was started on the third day.But inspite of all these measures, she was noticed to be lethargic and dehydrated.Other important observation was significant polyuria (urine output > 5 ml/kg/hour).
Investigations including sepsis screen, serum urea/ creatinine, serum electrolytes and arterial blood gases revealed increased hematocrit, hyponatremia, hypokalemia, hypochloremia, slightly raised serum urea, normal creatinine, metabolic alkalosis and no evidence of infection as shown in Table I.She was stabilized with (I.V.) fluids and electrolytes for correction of dehydration and dyselectrolytemia.Keeping in view above mentioned laboratory investigations and clinical picture, she was suspected for ABS.Urinary estimation of Na + , K + , Cl -and Ca ++ revealed markedly raised urinary levels of all these electrolytes as shown in Table I.Ultrasonography of abdomen and brain revealed unremarkable study.She was progressively weaned off I.V. fluids with increased NG feeds and oral supplementation of Na,Cl and potassium.Her serum electrolytes and dehydration was corrected as shown by serial monitoring (Table I).She started gaining weight on NG feeds.But she could not tolerate oral feeds and polyuria persisted.On the 20th day, her weight was 1.7 kg, serum aldosterone and serum renin levels were also reported very high (Table I).She was started with indomethacin orally (2 mg/kg/day) but polyuria was not controlled.She was improving and gaining weight (1.8 kg on 25th day).But on 26th day, she had sudden cardiopulmonary arrest and could not be revived inspite of resuscitation.

DISCUSSION
Antenatal Bartter syndrome is a rare but important cause of polyhydramnios between 24 -30 weeks leading to premature delivery as in this case. 5Antenatal diagnosis is possible by documenting high chloride content of amniotic fluid and mutational analysis of genomic DNA extracted from cultured amniocytes obtained by amniocentesis.These patients can be treated antenatally by indomethacin which improves the prognosis. 6our different types have been described depending on type of genes involved in defective synthesis of proteins responsible for transport of various ions across tubular cells. 7Genes reported so far are SLC12A1 (NKCC2) gene residing in chromosome 15q15-q21 (type-1), ROMK (KCNJ1) gene located on 11q24-25 (type 2) and BSND gene which encodes the common accessory B-SUBMIT Barttin for CIC-Ka and CIC-Kb chloride channel (type-4).Several mutations of gene SLC12A1 have been reported but mutational analysis could not be done in this case due to lack of facilities.
Postnatally these patients have hyposthenuria and rapid weight loss.Major derangements are severe dehydration, hyponatremia, hypochloremia, hypokalemia and metabolic alkalosis.Correction of dehydration and meticulous management of electrolyte derangements is of vital importance for survival and growth of these babies. 1 They are likely to develop nephrocalcinosis in later life due to hypercalciuria.Prostaglandin synthesis inhibitors are usually required for disease control.Generally use of indomethacin (1 -5 mg/kg/day) is effective in reducing polyuria and correcting other electrolyte derangements.Other agent used are iboprufen (30 mg/kg/day), ketoconazole (20 mg/kg/day) or acetylsalicylic acid (100 mg/kg/day). 8is management reduces mortality, growth failure and nephrocalcinosis, but long-term outcome is still guarded.Some cases are so severe that they do not respond to these measures as in this case and succumb to electrolytes derangements and arrhythmias.These facts have been strongly substantiated in literature.Chan has comprehensively reviewed clinical features of Bartter syndrome by analyzing selected key references together with a PubMed search of literature from 2000 to 2011. 9t was concluded that patients with Bartter syndrome types 1, 2 and 4 present at a younger age than classic type.They present with symptoms, often quite severe in the neonatal period as was in this reported case.The severe, steady-state hypokalemia in Bartter syndrome may abruptly become life threatening under certain aggravating conditions.Clinicians need to be cognizant of such renal tubular disorders and promptly treat at-risk patients.
Antenatal diagnosis can be made.If Bartter gene is found, the fetus can be aborted.In case the fetus is not affected, pregnancy can be continued with a favourable outcome.Postnatally, early diagnosis and meticulous management is mandatory for survival and normal outcome of these patients.This case is reported to alert obstetricians and paediatricians about the existence of this important problem in our setup.So far, we have found one case reported in our national literature from the Aga Khan Hospital. 10eed for alertness is further warranted due to higher rate of consanguinity in our society.Mode of inheritence is autosomal recessive.Genetic counselling for future pregnancies is helpful in improving outcome for the affected families.

Table I :
Serial serum biochemistry values on.