Differential diagnosis of perinatal Bartter, Bartter and Gitelman syndromes

Abstract

The common finding of hypokalemic alkalosis in several unrelated disorders may confound the early diagnosis of salt-losing tubulopathy (SLT). Antenatal Bartter syndrome (BS) must be considered in idiopathic early-onset polyhydramnios. Fetal megabladder in BS may allow its distinction from third-trimester polyhydramnios that occurs in congenital chloride diarrhea (CCD). Fetal megacolon occurs in CCD while fecal chloride >90 mEq/L in infants is diagnostic. Failure-to-thrive, polydipsia and polyuria in early childhood are the hallmarks of classic BS. Unlike BS, there is low urinary chloride in hypokalemic alkalosis of intractable emesis and cystic fibrosis. Rarely, renal salt wasting may result from cystinosis, Dent disease, disorders of paracellular claudin-10b and Kir4.1 potassium-channel deficiency. Acquired BS may result from calcimimetic up-regulation of a calcium-sensing receptor or autoantibody inactivation of sodium chloride co-transporters in Sjögren syndrome. A relatively common event of heterozygous gene mutations for Gitelman syndrome increases the likelihood of its random occurrence in certain diseases of adult onset. Finally, diuretic abuse is the most common differential diagnosis of SLT. Unlike the persistent elevation in BS, urinary chloride concentration losses waxes and wanes on day-to-day assessment in patients with diuretic misuse.

Keywords: Gitelman; acquired Bartter; antenatal Bartter; hypochloremic metabolic alkalosis; pseudo-Bartter syndromes.

FIGURE 1

Deficits in Electrolyte Transport from the Renal Tubular Lumen across the Thick Ascending Limb of the Loop of Henle Cell Accounting for Types I, II, III, IV and V Bartter Syndrome.

FIGURE 2

Deficits in Electrolyte Transport from the Renal Tubular Lumen across the Principal Cell of the Early Distal Convoluted Tubule accounting for Gitelman Syndrome and EAST/ SeSAME Syndrome.

FIGURE 3

Pattern of Electrolyte Transport Across the Principal Cell, Intercalated Type A Cell and Intercalated Type B Cell of the Late Distal Tubule/ Cortical Collecting Ducts.

FIGURE 4

Algorithm for the Differential Diagnosis of Hypochloremic Metabolic Alkalosis.