Bartter's syndrome

The term tubular dysfunction with hypokalemia includes Bartter syndrome (including the Gitelman variant), pseudohypoaldosteronism (Liddle syndrome), and prenatal hyperprostaglandin E syndrome. The latter is not observed in adults.

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Causes Bartter's syndrome

Bartter syndrome is a genetically determined disease characterized by hypokalemia, metabolic alkalosis, hyperuricemia, and increased renin and aldosterone activity.

The Gitelman variant is singled out separately: in addition to the above-mentioned symptoms, hypomagnesemia and hypocalciuria are also noted.

At present, some genetic mechanisms of Bartter syndrome and Gitelman variant have been deciphered. Bartter syndrome is inherited in an autosomal recessive manner, while Liddle syndrome is inherited in an autosomal dominant manner. Mutations responsible for the development of Liddle syndrome have been identified (16p12.2-13.11 and 12p13.1).

Variants of Bartter syndrome

Option	Localization of mutation	Gene product
Type I (neonatal)	NKCC2(15q)	Furosemide-, bumetanide-sensitive Na + -, K + -, 2C1-transport protein of the ascending limb of the loop of Henle
Type II	ROMK(llq24)	ATP-dependent potassium channel protein
Type III	CLKNKB (1р36)	Transporter protein C1
Gitelman's variant	NCCT(16ql3)	Thiazide-sensitive Na + and C1 transporter

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Symptoms Bartter's syndrome

Bartter syndrome, which manifests itself in early childhood (neonatal variant), is characterized by a severe course with polyuria, dehydration, hyperthermia, hypercalciuria and early development of calcium nephrolithiasis.

Bartter syndrome, manifested later (classic variant), is more benign. Most patients begin to complain before the age of 25. Typical symptoms of Bartter syndrome are signs of hypokalemia: muscle weakness, paresthesia, muscle cramps up to typical convulsions.

With severe hypokalemia, rhabdomyolysis may develop, complicated by acute renal failure, but such observations are rare. In Bartter syndrome, blood pressure remains normal, and polyuria is often observed.

The Gitelman variant is often first detected in adults. Hypomagnesemia causes calcification of the articular cartilage, leading to persistent arthralgia. Calcium deposits in the sclera and iris are also observed. Terminal renal failure sometimes develops. In patients with the Gitelman variant, continuous ambulatory peritoneal dialysis should be preferred, as it is associated with a lower risk of further electrolyte metabolism disorder.

Liddle syndrome is characterized by severe arterial hypertension.

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Diagnostics Bartter's syndrome

Laboratory diagnostics of Bartter syndrome

In both the “classic” Bartter syndrome and the Gitelman variant, a significant increase in the concentration of potassium and chlorides in the urine is noted.

In Liddle's syndrome, there is a marked increase in potassium excretion with simultaneous sodium retention. The concentration of aldosterone in the blood is unchanged or decreased.

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Instrumental diagnostics of Bartter syndrome

Unlike Bartter syndrome, in the Gitelman variant, hyperplasia of the juxtaglomerular apparatus is not detected in renal tissue biopsies.

Treatment Bartter's syndrome

Due to the increased activity of prostaglandins, treatment of Bartter syndrome involves the administration of NSAIDs. When prescribing them, it should be taken into account that the risk of developing nephrotoxic effects is higher than in the general population.

Patients with pseudohypoaldosteronism are prescribed triamterene or amiloride. Spironolactone is ineffective; loop and thiazide-like diuretics are contraindicated due to worsening hypokalemia. If terminal renal failure develops, kidney transplantation is performed.