Bartter's Syndrome

The term tubular dysfunction with hypokalemia combines Bartter's syndrome (including the Gitelman variant), pseudohyperdosteronism (Liddl's syndrome), and prenatal hyperprostaglandin E syndrome. The latter is not observed in adults.

[1], [2], [3], [4]

Causes of the bartter syndrome

Bartter's syndrome is a genetically determined disease manifested by hypokalemia, metabolic alkalosis, hyperuricemia and increased activity of renin and aldosterone.

Separately, Gitelman's variant is singled out: in addition to these features, hypomagnesemia and hypocalcauria are also noted.

At present, some genetic mechanisms of the Bartter syndrome and the Gitelman variant have been deciphered. Bartter's syndrome is inherited by autosomal recessive, Liddle syndrome - by autosomal dominant type. Identified mutations responsible for the development of Liddle syndrome (16p12.2-13.11 and 12p13.1).

Options for Bartter's Syndrome

Option	Localization of the mutation	The gene product
Type I (neonatal)	NKCC2 (15q)	Furosemide, bumetanide-sensitive Na + -, K + -, 2C1 transport protein of the ascending knee of the Henle loop
Type II	ROMK (llq24)	ATP-dependent potassium channel protein
Type III	CLKNKB (1p36)	Protein-transporter C1
Gitelman's version	NCCT (16ql3)	The thiazide sensitive transporter Na +  and C1

[5], [6], [7], [8], [9]

Symptoms of the bartter syndrome

For Bartter's syndrome, manifested in early childhood (neonatal variant), a severe course with polyuria, dehydration, hyperthermia, hypercalciuria and early development of calcium nephrolithiasis is characteristic.

The Bartter syndrome, which later manifested itself (the classical version), proceeds more benignly. Most patients start complaining before the age of 25. Typical symptoms of Bartter's syndrome are signs of  hypokalemia : muscle weakness, paresthesia, muscle cramps up to typical seizures.

With severe hypokalemia, rhabdomyolysis, complicated by acute renal failure, is possible, but such observations are rare. With Bartter's syndrome, blood pressure remains normal, polyuria is often observed  .

The Gitelman variant is often first discovered in an adult. Hypomagnesemia causes calcification of articular cartilage, resulting in permanent arthralgia. Also, calcium deposition in the sclera and iris of the eye is observed. Sometimes terminal renal failure develops. In patients with the Gitelman variant, preference should be given to continuous outpatient peritoneal dialysis, which is associated with a lower risk of further disturbance of the metabolism of electrolytes.

For Liddle syndrome characterized by severe arterial hypertension.

[10], [11], [12], [13]

Diagnostics of the bartter syndrome

Laboratory Diagnosis of Bartter's Syndrome

As with the "classic" Bartter syndrome, and with the Gitelman variant, a significant increase in the concentration of potassium and chloride in the urine is noted.

With Liddle's syndrome, a marked increase in the excretion of potassium with a simultaneous sodium retention is observed. The concentration of aldosterone in the blood is not changed or reduced.

[14], [15]

Instrumental Diagnosis of Bartter's Syndrome

Unlike Bartter's syndrome, Gitelman's variant in the biopsy specimens of the kidney tissue does not show hyperplasia of the juxtaglomerular apparatus.

Treatment of the bartter syndrome

In connection with the increase in prostaglandin activity, the treatment of Bartter's syndrome consists in the administration of NSAIDs. At their appointment it is necessary to consider, that the risk of development of nephrotoxic action is higher, than in the general population.

Patients with pseudo-hypoaldosteronism are assigned triamterene or amiloride. Spironolactone is ineffective; loop and thiazide-like diuretics are contraindicated because of aggravation of hypokalemia. With the development of terminal renal failure, kidney transplantation is performed.