Bartter's Syndrome

This is an unusual but important congenital 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 hypokalemic alkalosis without oedema.¹

It is an heterogeneous entity with at least 2 subsets:

1. Hypokalemic alkalosis with hypercalciuria (true Bartter's Syndrome) and
2. Hypokalemic alkalosis with hypocalciuria (Gitelman's syndrome)

• Rare genetic disorder - incidence estimated at 1.2 per million population²
• Gitleman's is relatively more common than Bartter's syndrome³
• No racial or gender preference

The primary problem is loss of excessive amounts of sodium and potassium in the urine. This leads to hypovolaemia and secondary hyperaldosteronism.

• True Bartter patients usually present >5 years with signs of vascular volume depletion, polyuria, and polydipsia; while Gitelman's syndrome patients typically present at older ages without overt hypovolemia 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 and neuromuscular irritability may occur especially in Gitelman's syndrome.²
  • 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.⁴
• 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).⁵
• 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, hypochloremic metabolic alkalosis, and increased urinary K+ and Cl- (but normal BP 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.⁶

• Electrolyte replacement e.g. potassium, magnesium and sometimes sodium. This needs to be individualised and depends on symptoms.²
• NSAIDs and selective COX-2 inhibitors have also been used.³
• Other treatments have also been tried with differing results e.g. potassium sparing diuretics e.g. amiloride, ACEIs, spironolactone and eplerenone.²

There has been reports of progressive renal impairment in Bartter's and Gitelman's syndrome. This may relate to chronic hypokalemia (which can cause tubulo-interstitial damage) or glomerulosclerosis.²

• 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.
• Hillel J. Gitelman described the variant in 1966 which presents at a later age than Bartter's and with hypocalciuria.