The portal for rare diseases and orphan drugs

Exact prevalence of Classic Bartter syndrome is not known. It is by far the most frequent type of Bartter syndrome.

Classic Bartter syndrome is characterized by a milder clinical picture with a wide phenotypic heterogeneity when compared to other subtypes of Bartter syndrome. Only one third of the patients present with maternal polyhydramnios which usually does not lead to prematurity. Patients usually present after neonatal period with failure to thrive, fatigue, muscle weakness, cramps and carpopedal spasms. Hypokalemia and alkalosis are common. Polyuria and hypostenuria/isosthenuria are variable, as is hypercalciuria. Few patients develop medullary nephrocalcinosis.

Mutation in CLCNKB gene (1p36), encoding a basolateral chloride channel ClCKb, has been identified as the most frequent cause of classic Bartter syndrome. Both the chloride channels, ClCKa and ClCKb are expressed in thick ascending limb of the loop of Henle (TALH), ClCKa is exclusively expressed in the ascending limb, while ClCKb is also expressed in distal convoluted tubule (DCT), thereby explaining the pronounced DCT features (similar to Gitelman syndrome; see this term) in some patients with CLCNKB mutations. CLCNKB mutations define classic Bartter syndrome; however, genes other than CLCNKB (those that are usually associated with other types of Bartter syndrome) may less commonly cause the classic, less severe phenotype, such as SLC12A1 and KCNJ1. Rarely, patients with BSND mutation may show a mild phenotype of salt loss associated with deafness.

Diagnosis is based on the clinical picture, plasma and urine electrolytes (sodium, potassium, chloride, bicarbonate, magnesium, calcium), renin and aldosterone levels. Calcium levels in the urine may be normal or slightly increased. Genetic testing provides the definite diagnosis.

The differential diagnosis includes pseudo-Bartter syndrome (diuretic abuse, surreptitious vomiting), cystic fibrosis, Gitelman syndrome, and celiac disease (see these terms).

Diagnostic testing of amniocytes might be indicated for mothers of affected children, or potential heterozygous carriers (close relatives of affected individuals).

Inheritance is autosomal recessive.

Treatment includes oral potassium supplements, non-steroidal anti-inflammatory drugs (e.g. indometacin) and possibly potassium-sparing diuretics. In stressful situations (additional diseases, surgical procedures, trauma) blood electrolyte levels may change rapidly, requiring prompt and vigorous treatment.

Life expectancy may be reduced in severe cases but renal failure is rare. Quality of life may be poor, growth rate reduced, and medicalization/hospitalization rate high.