Disease relevance of Bartter Syndrome

• Hyperprostaglandin E syndrome/antenatal Bartter syndrome is accompanied by a pathologically elevated synthesis of prostaglandin E(2), thought to be responsible for aggravation of clinical symptoms such as salt and water loss, vomiting, diarrhea, and failure to thrive [1].
• In this study administration of the cyclooxygenase-2 (COX-2) specific inhibitor nimesulide to patients with hyperprostaglandin E syndrome/antenatal Bartter syndrome blocked renal prostaglandin E(2) formation and relieved the key parameters hyperprostaglandinuria, secondary hyperaldosteronism, and hypercalciuria [1].
• Hypercalciuric Bartter syndrome: resolution of nephrocalcinosis with indomethacin [2].
• It is thus suggested that polyhydramnios is the result of increased fetal urine output in Bartter syndrome and that amniotic fluid aldosterone is a reliable marker for the prenatal diagnosis of this condition [3].
• The possible role of NO and AM in maintaining this reduced vascular reactivity was examined by studying plasma and urinary nitrite, a stable metabolite of NO, and AM levels in ten children with Bartter syndrome, ten healthy controls, and five children with hypokalemia of causes other than Bartter syndrome (pseudo-Bartter) [4].

High impact information on Bartter Syndrome

• pH gating of ROMK (K(ir)1.1) channels: control by an Arg-Lys-Arg triad disrupted in antenatal Bartter syndrome [5].
• Linkage of infantile Bartter syndrome with sensorineural deafness to chromosome 1p [6].
• The inwardly rectifying K+ channel, Kir1.1 (ROMK) appears to form the pore of the channel, and mutations in Kir1.1 are responsible for Bartter syndrome [7].
• Loss of function mutations in kidney Kir1.1 (renal outer medullary potassium channel, KCNJ1) inwardly rectifying potassium channels can be found in patients suffering from hyperprostaglandin E syndrome (HPS), the antenatal form of Bartter syndrome [8].
• Dominant role of prostaglandin E2 EP4 receptor in furosemide-induced salt-losing tubulopathy: a model for hyperprostaglandin E syndrome/antenatal Bartter syndrome [9].

Chemical compound and disease context of Bartter Syndrome

• Human CLC-KB has been identified as a kidney-specific member of the CLC chloride channel family, and mutations of the human CLC-KB gene are known to cause Bartter syndrome type III [10].
• Increased formation of prostaglandin E2 (PGE2) is a key part of hyperprostaglandin E syndrome/antenatal Bartter syndrome (HPS/aBS), a renal disease characterized by NaCl wasting, water loss, and hyperreninism [9].
• Amelioration of the clinical symptoms by use of nimesulide indicates that COX-2 may play an important pathogenetic role in hyperprostaglandin E syndrome/antenatal Bartter syndrome [1].
• In addition to findings typically seen in patients with Bartter syndrome or hyperprostaglandin E syndrome, she had massive urinary excretion of prostaglandins E2 and E-M, normal calcium metabolism, hyperphosphaturia, and severe hyperchloriduria and hyperkaliuria with limited response to indomethacin [11].
• Although certain aspects of this condition resemble Bartter syndrome, the low concentrations of aldosterone and the absence of evidence for mineralocorticoid excess suggest a previously undescribed syndrome [12].

Biological context of Bartter Syndrome

• These cases represent the first report of the simultaneous presence of heterozygous and compound heterozygous mutations in the SLC12A3 and CLCNKB genes, both of which are involved in renal salt losing tubulopathies, and confirm previous observations regarding classic Bartter syndrome phenotype variability in the same kindred [13].
• METHODS: By haplotype analysis we demonstrate linkage to this locus in nine consanguineous families with antenatal Bartter syndrome associated with sensorineural deafness [14].
• BACKGROUND: Recently a locus for antenatal Bartter syndrome associated with sensorineural deafness was mapped to human chromosome 1p31 in a single consanguineous Bedouin family (Brennan et al. Am J Hum Genet 1998; 62: 355-361) [14].
• Elevated aldosterone in amniotic fluid and maternal blood has diagnostic potential in pregnancies complicated with a fetus of Bartter syndrome [15].
• Despite sharing a common mutation, the clinical manifestations of the syndrome in the patients varied from lack of symptoms to severe growth retardation.Demonstration of a point mutation within the CLCNKB gene as the apparently unique cause of Bartter syndrome type III in Spain is highly suggestive of a founder effect [16].

Anatomical context of Bartter Syndrome

• Because PGE2 is known to inhibit the response of lymphocytes to phytohemagglutinin, we postulate that PGE2 may mediate the reduced blastogenic response observed in patients with Bartter syndrome [17].

Gene context of Bartter Syndrome

• A new distinct group in Bartter syndrome accompanied by sensorineural deafness (BSND) has been identified among the IBS patients [18].
• Pathogenetic role of cyclooxygenase-2 in hyperprostaglandin E syndrome/antenatal Bartter syndrome: therapeutic use of the cyclooxygenase-2 inhibitor nimesulide [1].
• RECENT FINDINGS: Previously, three genes (SLC12A2, the sodium-potassium-chloride co-transporter; KCNJ1, the ROMK potassium ion channel; ClC-Kb, the basolateral chloride ion channel) had been identified as causing antenatal and 'classic' Bartter syndrome [19].
• A Spanish founder mutation in the chloride channel gene, CLCNKB, as a cause of atypical Bartter syndrome in adult age [20].
• Inactivating mutations in three members of the SLC12 gene family result in Mendelian disease; Bartter syndrome type I in the case of SLC12A1, Gitelman syndrome for SLC12A3, and peripheral neuropathy in the case of SLC12A6 [21].

Analytical, diagnostic and therapeutic context of Bartter Syndrome

• With early diagnosis and treatment with indomethacin plus adequate water, calories, and sodium, normal growth can be achieved and nephrocalcinosis may be prevented in children with neonatal Bartter syndrome [22].

References