What is Bartter’s syndrome?

Bartter’s syndrome

Bartter’s syndrome is an inherited condition (usually autosomal recessive), clinically similar to the chronic use of loop diuretics e.g Furosemide, Bumetanide etc, resulting in severe Hypokalemia associated with normotension.

Pathogenesis of Bartter’s syndrome:

In Bartter’s syndrome, the primary defect is impairment in sodium and chloride reabsorption from the thick ascending limb of the loop of Henle. There may be a mutation in any one of the genes encoding, NKCC2 (Na-K-2Cl) channel, the ATP regulated ROMK (renal outer medullary potassium) channel or kidney-specific basolateral chloride (ClC-kb) channels

Types of Bartter’s syndrome:

There are 4 types of Bartter’s syndrome according to the loss of function of the above-mentioned channels:

Type 1: Mutation in gene encoding NKCC2 (Na-K-2Cl) channel

Type 2: Mutation in gene encoding ATP regulated ROMK (renal outer medullary potassium) channel

Type 3: Mutation in gene encoding kidney-specific basolateral chloride (ClC-kb) channels

Type 4: Loss-of-function mutations of BSND (Bartter’s syndrome with sensorineural deafness) gene which encodes Barttin, a β–subunit for ClC-ka and ClC-kb chloride channels. Type 4 of Bartter’s syndrome is associated with sensorineural deafness and renal failure.

Clinical classification of Bartter's syndrome:

Antenatal Bartter's syndrome: The more severe form of Bartter's syndrome due to the mutations in NKCC2, ROMK, or Barttin. It typically presents in the perinatal period (e.g in the newborn)
Classic Bartter syndrome: The milder variety, caused by the mutations of ClC-Kb. It develops normally during the first 2 to 5 years of life. 

Clinical features and laboratory findings of Bartter’s syndrome:

• Presents in the neonatal period or early childhood with polyuria, polydipsia, salt craving, and growth retardation
• Normotension
• Hypokalemia
• hypochloremic metabolic alkalosis
• Hypercalciuria with nephrocalcinosis
• Occasional hypomagnesaemia
• Increased renin and aldosterone
• Increased urinary prostaglandin excretion
• Chronic kidney disease from nephrocalcinosis or from tubular atrophy (in those patients with severe Bartter's syndrome who survive early childhood )
• Interstitial fibrosis from severe persistent hypokalemia

N.B: The features of Bartter’s’ syndrome is similar to that of chronic use of loop diuretics.

Diagnosis of Bartter’s syndrome:

• High urinary potassium and chloride despite low serum values
• Increased plasma renin (remember,  in primary aldosteronism, renin levels are low)
• Hyperplasia of the juxtaglomerular apparatus is seen on renal biopsy (careful exclusion of diuretic abuse is necessary).
• Hypercalciuria is a common feature
• Magnesium wasting, though rare also occurs

Treatment of Bartter’s syndrome:

It needs combinations of potassium and magnesium supplements (lifelong), amiloride, and indomethacin is effective by inhibiting excess prostaglandin synthesis.

Additional

Why there is normal blood pressure in Bartter’s syndrome?

Ans: There is an increased intra-renal production of prostaglandin E₂. This is secondary to sodium and volume depletion, Hypokalemia and the consequent neuro-humoral response rather than a primary defect. PGE₂ causes vasodilatation and may explain why the blood pressure remains normal.