Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Antenatal Bartter syndrome type 1

Antenatal Bartter syndrome is characterized by polyuria that starts before birth, which signifies by polyhydramnios. The molecular genetic background are autosomal recessive inactivating mutations of the SLC12A1 gene.

Epidemiology

Although exact figures still unknown and difficult to obtain, the the incidence is thought between 1 in 50,000 to 1 in 100,000.

Clinical Findings

The clinical diagnosis is suspected when polyhydramnios is observed since about the 25th week of gestation. It may require amniocentesis. Renine and aldosterone levels are elevated in the amniotic fluid. Often polyhydramnios causes preterm delivery. Beginning with the first day of life excessive water and salt losses originates additional systemic clinical problems such as fever, vmoting, and diarrhoea.

Besides the typical Bartter symptoms (hypokalemia, metabolic alkalosis, hyperreninemic hyperaldosteronism, normal blood pressure, and hyperkaliuria), antenatal Bartter syndrome is characterized by hypercalciuria that brings about nephrocalcinosis often seen in utero already.

Indometacine therapy is highly effective and sometimes prevents spironolactone or potassium supplementation.

Growth retardation is common and there are patients in which it becomes impossible to maintain normal biochemical parameters.

Diagnosis

The diagnosis requires a thorough study of all solutes in plasma and urine as it is required for all Bartter syndromes. Additionally urine levels of prostaglandines PGE2 und PGF2alpha are helpful.

Molecular genetic testing allows to differentiate the exact type of Bartter syndrome which has implications for disease management.

Symptoms

Polyhydramnios
Polyhydramnios in antenatal Bartter syndrome often is so prominent that relief is sought by paracentesis.
Nephrocalcinosis
Nephrocalcinosis in antenatal Bartter syndrome results from hypercalciuria and is accompanied by hypokalemia and metabolic alkalosis.
Hypercalciuria
Hypercalciuria in antenatal Bartter syndrome causes nephrocalcinosis. Furthermore renal salt an water wastage dominate the clinical picture. Hypokalemia and metabolic alkalosis are the most prominent clinical symptoms.

Systematic

Bartter syndrome
Antenatal Bartter syndrome type 1
SLC12A1
Antenatal Bartter syndrome type 2
Classic Bartter syndrome
Hypercalciuric hypocalcemia 1
Hypercalciuric hypocalcemia 2
Infantile Bartter syndrome with deafness type 4
Transient antenatal Bartter syndrome

References:

1.

et al. (1997) Mutations in the gene encoding the inwardly-rectifying renal potassium channel, ROMK, cause the antenatal variant of Bartter syndrome: evidence for genetic heterogeneity. International Collaborative Study Group for Bartter-like Syndromes.

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2.

Peters M et al. () Hereditary Hypokalemic Salt-losing Tubular Disorders.

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3.

Colussi G et al. (2007) A thiazide test for the diagnosis of renal tubular hypokalemic disorders.

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4.

Sassen MC et al. (2007) Can renal tubular hypokalemic disorders be accurately diagnosed on the basis of the diuretic response to thiazide?

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5.

Seyberth HW et al. (1987) Role of prostaglandins in hyperprostaglandin E syndrome and in selected renal tubular disorders.

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6.

Seyberth HW et al. (1985) Congenital hypokalemia with hypercalciuria in preterm infants: a hyperprostaglandinuric tubular syndrome different from Bartter syndrome.

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7.

Proesmans W et al. () Bartter syndrome in two siblings--antenatal and neonatal observations.

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8.

Deschenes G et al. (1993) [Antenatal form of Bartter's syndrome]

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9.

Simon DB et al. (1996) Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2.

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Update: Sept. 26, 2018