Genotype/phenotype observations in African Americans with Bartter syndrome

Background: Two Bartter syndrome phenotypes have been described, and molecu lar analyses demonstrate mutation in 1 of 3 genes encoding ascending limb o f Henle transporters. We report phenotypic observation in 4 African America n children with Bartter syndrome in the context of a distinct genotype. Methods: Mutation analyses were performed in 5 unrelated African American c hildren with Batter syndrome. These results were correlated to clinical and laboratory data. Calcium metabolism was evaulated with a bone disk bioassa y. Results: Mutation anaylses demonstrated homozygous deletion of the ClC-Kb g ene in all children. Two children had polyhydramnios and premature birth; t he others were born at term and presented with failure to thrive or dehydra tion. All received indomethacin, spirolactone, and potassium chloride with improved but borderline hypokalemia. Growth has improved with therapy, but height SD scores range from -3.9- to 1.4. Urinary calcium excretion is norm al, and bone disk bioassay shows no abnormal calciotropic activity. No pati ent had nephrocalcinosis, but renal sonograms show loss of corticomedullary differentiation. Conclusions: African Americans with Bartter syndrome genotyped to date have homozygous deletion of ClC-Kb. Clinical observations in our patients inclu de partial correction of hypokalemia and suboptimal growth despite therapy. Abnormal calciotropic activity and nephrocalcinosis are not seen but renan ultrasounds are abnormal.