The antenatal form of Bartter syndrome is a life-threatening disorder in which both renal tubular hypokalemic alkalosis and profound systemic symptoms are manifest (Seyberth et al., 1985; Deschenes et al., 1993; and Proesmans et al., 1985). The abnormalities ... The antenatal form of Bartter syndrome is a life-threatening disorder in which both renal tubular hypokalemic alkalosis and profound systemic symptoms are manifest (Seyberth et al., 1985; Deschenes et al., 1993; and Proesmans et al., 1985). The abnormalities begin in utero with marked fetal polyuria that leads to polyhydramnios between 24 and 30 weeks of gestation and, typically, premature delivery (Ohlsson et al., 1984). The amniotic fluid contains high chloride levels but normal concentrations of sodium, potassium, calcium, and prostaglandin E2. Affected neonates have severe salt wasting and hyposthenuria, moderate hypokalemic metabolic alkalosis, hyperprostaglandinuria, and failure to thrive. The International Collaborative Study Group for Bartter-like Syndromes (1997) noted that an essential manifestation of the antenatal variant is marked hypercalciuria, and as a secondary consequence, affected infants develop nephrocalcinosis and osteopenia. Fever, vomiting, and occasional diarrhea associated with the disorder have been attributed to the stimulation of renal and systemic prostaglandin E2 activity in affected infants; these symptoms are effectively treated with inhibitors of prostaglandin synthesis. Based on these clinical features, the antenatal form of Bartter syndrome has been referred to as the hyperprostaglandin E syndrome (Seyberth et al., 1987). - Clinical Variability Kurtz et al. (1997) studied a cohort of 20 Costa Rican patients, previously described by Madrigal et al. (1997), who had a congenital syndrome that bore strong similarities to the antenatal Bartter syndrome type 1 but also had several distinct features. In all patients, pregnancy was complicated by polyhydramnios, and 7 of the 9 patients were born prematurely. Six of 9 patients studied in detail were presented for evaluation within the first year of life. One was not diagnosed until the age of 10 years and another was 4.5 years old at the time of diagnosis. All affected children had experienced recurrent episodes of vomiting and dehydration, dating from the first few weeks of life. The phenotype was remarkable for a peculiar facies in 7 of 9 children, characterized by a triangularly shaped face, protruding ears, and drooping mouth; in addition, 5 of 9 had strabismus, and there was evidence of sensorineural hearing loss by audiogram testing in 2 of 9. All had hypokalemic metabolic alkalosis, hyposthenuria, and failure to thrive, with growth parameters less than the third centile for age. Hypercalciuria with associated sonographic evidence of nephrocalcinosis was demonstrated in 7 children. The other 2 children had evidence of nephrocalcinosis but normal urine calcium excretion. Renal function was well preserved in all but 1 patient, who developed renal insufficiency and progressed to end-stage renal disease by 16 years of age. Although the development of tubulointerstitial disease leading to a progressive decline in renal function had been described both in patients treated with long-term indomethacin and in patients with classic Bartter syndrome, this patient was not treated with indomethacin, and the etiology of her end-stage renal disease remained unexplained. Kurtz et al. (1997) noted that the Costa Rican patients had a milder clinical course than other antenatal Bartter syndrome patients with NKCC2 (SLC12A1) mutations.
In 5 families with antenatal Bartter syndrome, Simon et al. (1996) identified frameshift or nonconservative missense mutations in the NKCC2 gene that cosegregated with the disease (see 600839.0001-600839.0003).
In 9 patients from 7 Costa Rican families ... In 5 families with antenatal Bartter syndrome, Simon et al. (1996) identified frameshift or nonconservative missense mutations in the NKCC2 gene that cosegregated with the disease (see 600839.0001-600839.0003). In 9 patients from 7 Costa Rican families with a variant form of antenatal Bartter syndrome type 1, Kurtz et al. (1997) analyzed the SLC12A1 gene and identified homozygosity for a nonsense mutation (600839.0003) in 3 patients; in 3 additional patients, the mutation was only detected on 1 allele. The mutant allele was contained on a single common haplotype, suggesting that most patients with antenatal Bartter syndrome in Costa Rica share a single common ancestor. Nozu et al. (2009) reported a 7-year-old Japanese girl with Bartter syndrome type 1 who was compound heterozygous for mutations in the SLC12A1 gene (600839.0004 and 600839.0005). The authors stated tha this was the first study to perform mutation analysis in inherited kidney disease using noninvasive methods, i.e., with cells from urinary sediment rather than renal biopsy.