Antenatal Bartter Syndrome

A phenotypic variant of Bartter syndrome presenting antenatally with maternal polyhydramnios, pre-term delivery and postnatally with polyuria, and nephrocalcinosis. Hypokalemic alkalosis, increased levels of plasma renin and aldosterone, low blood pressure and vascular resistance to angiotensin II are characteristically associated. Genotypically they comprise Type 1 and Type 2 Bartter syndrome

Epidemiology

Prevalence of antenatal Bartter syndrome is not exactly known but it comprises about half the cases of Bartter syndrome.

Clinical description

Typically, antenatal Bartter syndrome manifests prenatally with maternal polyhydramnios (due to fetal polyuria) usually evident by the end of second trimester, often leading to preterm labour and prematurity. Newborns present with life-threatening polyuria, isosthenuria/hyposthenuria, hyperprostaglandinuria, hypercalciuria and hypokalemic alkalosis. Virtually all patients develop medullary nephrocalcinosis within the first few weeks of life. Patients with type 2 genotype present with a transient hyperkalemic acidosis in the neonatal period; they later manifest with a less severe hypokalemic alkalosis.

Etiology

Type 1 Bartter syndrome is caused by mutations in the SLC12A1 (15q15-q21) encoding sodium-potassium-chloride co-transporter protein, NKCC2 whereas Type 2 Bartter syndrome is caused by mutations in KCNJ1 (11q24) encoding renal outer medullary potassium channel, ROMK.

Genetic counseling

The disease is transmitted in an autosomal recessive manner.