This is an unusual but important form of secondary hyperaldosteronism; due to abnormalities in renal handling of electrolytes. It is associated with hypertrophy and hyperplasia of the juxtaglomerular cells, normal blood pressure and hypokalaemic alkalosis without oedema.
It is an heterogeneous entity with at least 2 subsets:
- Hypokalaemic alkalosis with hypercalciuria (true Bartter's syndrome).
- Hypokalaemic alkalosis with hypocalciuria (Gitelman's syndrome).
- Prevalence varies from 1.2-1.7 per 100,000 population.
- Gitelman's syndrome is relatively more common than Bartter's syndrome.
- Consanguineous marriages are associated with a higher prevalence.
- There is no racial or gender preference.
- Bartter's syndrome can be diagnosed antenatally, in the early neonatal period, during childhood or adolescence.
- Gitelman's syndrome is not diagnosed until adolescence or early adulthood.
The primary problem is loss of excessive amounts of sodium and potassium in the urine. This leads to hypovolaemia and secondary hyperaldosteronism.
- True Bartter's syndrome patients usually present aged >5 years with signs of vascular volume depletion, polyuria, and polydipsia, while Gitelman's syndrome patients typically present at older ages without overt hypovolaemia as failure to thrive.
- Other features include:
- Short stature.
- Hyperactive renin-angiotensin system (plasma renin increased, lack of effect of angiotensin on blood pressure, renal potassium wasting, increased renal prostaglandin production and, occasionally, hypomagnesemia).
- Impaired urinary concentrating ability.
- Muscle weakness and neuromuscular irritability may occur especially in Gitelman's syndrome.
- It can also present in utero with resulting prematurity or polyhydramnios.
- The primary (autosomal recessive) defect lies in the active chloride reabsorption in the loop of Henle.
- Mutations occur in the luminal sodium-potassium-2-chloride co-transporter (antenatal Bartter's syndrome type I), the luminal potassium channel (antenatal Bartter's syndrome type II), or the basolateral chloride channel (classic Bartter's syndrome type III).
- Prostaglandins increase as a consequence of volume contraction, and this increase may itself stimulate renin secretion.
- Prematurity, polyuria, dehydration, and growth retardation are to a large extent caused by high levels of prostaglandins. Selective and specific COX-2 inhibitors are available. This isoenzyme seems to be responsible for the elevated levels of inducible prostaglandins from the macula densa and the thick ascending limb of Henle's loop, hence their use in Bartter's syndrome.
- Biochemistry reveals hypokalaemia, hypochloraemic metabolic alkalosis, and increased urinary K+ and Cl- (but normal blood pressure and no oedema).
- In Bartter's syndrome there is normocalcaemia and normomagnesaemia.
- Hypomagnesaemia is seen in Gitelman's syndrome.
- 12-lead ECG - half of Gitelman's syndrome patients have prolonged QT interval. This can lead to ventricular tachycardia and sudden death.
- Electrolyte replacement, eg potassium, magnesium and sometimes sodium. This needs to be individualised and depends on symptoms.
- Non-steroidal anti-inflammatory drugs and selective COX-2 inhibitors have also been used.
- Other treatments have also been tried with differing results; for example, potassium-sparing diuretics - amiloride, angiotensin-converting enzyme inhibitors, spironolactone and eplerenone.
There have been reports of progressive renal impairment in Bartter's syndrome and Gitelman's syndrome. This may relate to chronic hypokalaemia (which can cause tubulo-interstitial damage) or glomerulosclerosis.
Frederic Crosby Bartter first described the syndrome of hypokalaemia, alkalosis, hyperaldosteronism and juxtaglomerular hyperplasia with normal blood pressure in two patients aged 5 and 25 years. In 1966, Hillel J Gitelman described the variant which presents at a later age than Bartter's syndrome and with hypocalciuria.
Further reading & references
- Bartter FC, Pronove P, Gill JR Jr, et al; Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndrome. Am J Med. 1962 Dec;33:811-28.
- Frasetto LA et al; Bartter Syndrome, eMedicine, Sept 2009
- O'Shaughnessy KM, Karet FE; O'Shaughnessy KM, Karet FE; Salt handling and hypertension. Annu Rev Nutr. 2006;26:343-65.
- Unwin RJ, Capasso G; Bartter's and Gitelman's syndromes: their relationship to the actions of loop and thiazide diuretics. Curr Opin Pharmacol. 2006 Apr;6(2):208-13. Epub 2006 Feb 20.
- Kleta R, Basoglu C, Kuwertz-Broking E; New treatment options for Bartter's syndrome. N Engl J Med. 2000 Aug 31;343(9):661-2.
- Bartter Syndrome, Online Mendelian Inheritance in Man (OMIM); different forms of Bartter Syndrome
- Pachulski RT, Lopez F, Sharaf R; Gitelman's not-so-benign syndrome. N Engl J Med. 2005 Aug 25;353(8):850-1.
- Zanolari Calderari M, Vigier RO, Bettinelli A, et al; Electrocardiographic QT prolongation and sudden death in renal hypokalemic Nephron. 2002 Aug;91(4):762-3.
|Original Author: Dr Gurvinder Rull||Current Version: Dr Gurvinder Rull|
|Last Checked: 26/10/2010||Document ID: 1847 Version: 22||© EMIS|
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