Address for Correspondence: Dr. Rahul P. Bhamkar, Flat No. 9, Nest Building, Sector 1, Kalamboli, Navi Mumbai. India.
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Gitelman's Syndrome :

It also has milder course and later age of onset (6-13 yrs). Patients present with fatigue, muscle weakness and recurrent episodes of tetany in the form of carpopedal spasm. They don't have history of polyhydramnios and premature birth. What distinguishes them from BS is the presence of hypomagnesemia and hypocalciuria instead of hypercalciuria, the reason for which is not clear. Hypomagnesemia is probably due magnesium wasting in distal convoluted tubule due to inhibition of magnesium uptake in presence of hypokalemia.

Pseudo bartter's Syndrome :

These include group of condition in which there is hypokalemic metabolic alkalosis with no pathology in renal tubules hence the name "Pseudo bartter's Syndrome". Such conditions include cystic fibrosis, surreptitious diuretic use, chronic administration of chloride deficient diet, bulimia, cyclic vomiting, congenital chloride diarrhea and abuse of laxatives. Low chloride content in urine except in diuretic use exclude BS in these cases.

Table 1: Various types of Bartter's Syndromes and their characteristics

	Antenatal BS I	Antenatal BS II	Classic BS III	BS IV (BSND)	Gitelman's Variant
Channel	NKCC2	ROMK	CIC-Kb	CIC-Kb/ CIC-Ka	NCCT
Location	TAL	TAL, CD	TAL, DCT	TAL, Inner ear	DCT
Gene	SLC12A1	KCNJ1	CLCNKB	BSND	SLC12A3
Chromosome	15q15-21	11q24	1p36	1p31	16q13
Poly- hydramnios	Present	Present	Usually absent	Present	Absent
Gestational Age	Preterm	Preterm	Term	Preterm	Term
Age of onset	Antenatal	Antenatal	<1year	Antenatal	6-13 years
Symptoms	Polyuria	Polyuria	Hypokalemia Failure to thrive	Polyuria, Deafness	Hypokalemia, Tetany
Urine Ca excretion	High	High	Moderate	High	Hypocalciuria
Nephro-calcinosis	Present	Present	Usually absent	Present	Absent
Magnesium	Normal	Normal	Low or normal	Normal	Always Low
Prostaglandin level	Increased	Increased	Increased	Increased	Near Normal
Prostaglandin Excretion	Increased	Increased	Increased	Increased	Normal

Management :

Antenatal Diagnosis: Antenatal diagnosis should be done in a suspected case of unexplained polyhydramnios with history of consanguinity and previous affected sibling with Bartter's like illness. Identification of genetic mutation in sample obtained by amniocentesis at 18 weeks of gestation gives unequivocal diagnosis (6). Amniotic fluid biochemistry showing elevated chloride levels also helps in diagnosis.

Based on assumption of hyperprostaglandinism, antenatal and postnatal treatment of these patients with prostaglandin synthetase inhibitor, Indomethacin has shown promising results. Indomethacin should be started antenatally in a genetically diagnosed patient. Other causes of polyhydramnios like fetal intestinal losses, esophageal atresia should be excluded before initiation of therapy as in these cases indomethacin may aggravate the situation. Indomethacin therapy should be monitored carefully by fetal echocardiography and maternal serum indomethacin level because of complication like premature closure of ductus arteriosus, oliguric renal dysfunction, necrotizing enterocolitis, and ileal perforation (6). A low dose of indomethacin (0.5mg/kg/dose every 12 hourly) from 26-31 weeks of gestation is sufficient to arrest the progression of polyhydramnios. Other prostaglandin synthetase inhibitors like ibuprofen, acetylsalicylic acid have also been proved effective.

BS baby inspite of intrauterine polyuria and electrolyte loss, is well hydrated at birth because of compensation by placenta. But postnatally, there is rapid loss of electrolytes and fluids from the body. So immediate replacement is must. Indomethacin should be started in a low dose (0.2 mg/kg/day) as there is risk of acute renal failure and necrotizing enterocolitis.

Close monitoring of serum creatinine, urinary prostaglandin and serum indomethacin level is mandatory to detect drug toxicity and response to therapy. Dose can then be titrated to achieve adequate response. This therapy has shown to decrease polyuria, renal salt wasting, hyperprostaglandinuria, hypercalciuria and nephrocalcinosis.

References :

1. Bartter FC, Pronove P, Gill JR, Mac Cardle RC. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. Am J Med 1962; 33:811-28.
2. Peters M, Jeck N, Reinalter S et al. Clinical presentation of genetically defined patients with hypokalemic salt losing tubulopathies. Am J Med 2002; 112: 183-90.
3. Massa G, Proesman W, Devlieger H et al. Electrolyte composition of amniotic fluid in Bartter's syndrome. Eur J Obstet Gynecol Reprod Biol 1987; 24:355-40.
4. Modrigal G, Saborio P, Mora F, Rincon G, Guay-Woodford L. Bartter syndrome in Costa Rica: a description of 20 cases. Pediat Nephrol 1997; 11:296-301
5. Hanna S., Melly O, Leonid K, Daniel L. The Neonatal Variant of Bartter Syndrome and Deafness: Preservation of Renal Function. Pediatr 2003; 112:628-633.
6. Konrad M, Leonhardt, A, Hensen P, Seyberth HW, Kockerling A. Prenatal and postnatal management of hyperprostglandin E syndrome after genetic diagnosis from amniocytes. Pediatrics 1999; 103:678-683.

Last updated on 01-08-2008 Vol 5 Issue 8 Art # 30

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