BARTTER AND RELATED SYNDROMES - THE PUZZLE IS ALMOST SOLVED

It is now evident that the term Bartter syndrome does not represent a unique entity but encompasses a variety of disorders of renal electrol yte transport. Application of molecular biology techniques has permitt ed a better understanding of these ''Bartter-like syndromes,'' which a t present can be divided into three different genetic and clinical ent ities. Neonatal Bartter syndrome is observed in newborn infants and ch aracterized by polyhydramnios, premature delivery, life-threatening ep isodes of fever and dehydration during the early weeks of life, growth retardation, hypercalciuria, and early-onset nephrocalcinosis. Two mo lecular defects have been identified: either at the gene encoding the renal bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) or the gene encoding an ATP-sensitive inwardly rectifying K channel (ROMK). ''Clas sic'' Bartter syndrome is mostly observed during infancy and childhood and is characterized clinically by polyuria and growth retardation. N ephrocalcinosis is not present. Very recently, either deletions or mut ations at the gene encoding a renal chloride channel (CIC-Kb) have bee n identified. Gitelman syndrome is observed in older children and adul ts presenting with intermittent episodes of muscle weakness and tetany , hypokalemia, and hypomagnesemia. Mutations at the gene encoding the thiazide-sensitive Na-Cl co-transporter have been identified in the ma jority of patients studied. Obviously the validity of this classificat ion must be confirmed in the near future when all mutations have been described and genotypic-phenotypic correlations are better defined.