Bartter vrs Gitelman Syndrome

Question 1

BARTTER VERSUS GITELMAN SYNDROMES

Answer 1

Think furosemide (Bartter) versus thiazides (Gitelman). As these syndromes are equivalent to taking diuretics, they can induce salt loss and relative volume depletion, hence “compensatory” hyperrenin hyperaldosteronism without associated hypertension.

Question 2

BARTTER VERSUS GITELMAN SYNDROMES

Answer 2

As mutations of Bartter syndromes can lead to greater salt-wasting compared with Gitelman, hyperrenin and hyperaldosteronism are more marked in the former. Increased vasodilating prostaglandin E2 production is also thought to play a role in maintaining normotension in Bartter syndromes.

Question 3

BARTTER VERSUS GITELMAN SYNDROMES

Answer 3

Similar to taking diuretics, both Bartter and Gitelman syndromes are associated with hypokalemia and metabolic alkalosis.

Question 4

BARTTER VERSUS GITELMAN SYNDROMES

Mutations in Bartter Syndromes

Answer 4

Neonatal Bartter syndromes: types I (NKCC2) and II (ROMK—renal outer medullary K+ channel)

Question 5

BARTTER VERSUS GITELMAN SYNDROMES

Mutations in Bartter Syndromes

Answer 5

Classic Bartter syndrome: type III (ClC-Kb)

Question 6

BARTTER VERSUS GITELMAN SYNDROMES

Mutations in Bartter Syndromes

Answer 6

Bartter syndrome and sensorineural deafness (BSND): type IV Bartter (β-subunit of ClC-Ka and ClC-Kb); ClC-Ka is present in inner ear.

Question 7

BARTTER VERSUS GITELMAN SYNDROMES

Mutations in Bartter Syndromes

Answer 7

Calcium-sensing receptor (CaSR) gain-of-function mutation (inhibits ROMK): type V Bartter, associated with autosomal dominant hypocalcemia. Activation of CaSR inhibits ROMK activity

Question 8

BARTTER VERSUS GITELMAN SYNDROMES

Mutations in Bartter Syndromes

Answer 8

Question 9

BARTTER VERSUS GITELMAN SYNDROMES

Mutations in Bartter Syndromes

NOTE

Answer 9

K+ recycling back into the lumen via ROMK creates a positively charged lumen which facilitates divalent cation (Ca2+, Mg2+) reabsorption paracellularly. This process is facilitated by tight junction proteins claudin 16 and 19.

Question 10

BARTTER VERSUS GITELMAN SYNDROMES

Mutations in Bartter Syndromes

NOTE

Answer 10

Any transporter defect leading to suboptimal K+ recycling (e.g. loss of function mutation of ROMK or gain of function mutation of CaSR) or mutation of claudin 16/19 induces Ca2+ and Mg2+ wasting

Question 11

Mutation in Gitelman Syndrome Mutation of NCC a.k.a. TSC

Answer 11

Question 12

Clinical Manifestations of Bartter and Gitelman Syndrome

Answer 12

Question 13

NOTE

Answer 13

CLC-Kb is present in both loop of henle and distal convoluted tubule. This may explain minimal or absence of nephrocalcinosis in classic Bartter and BSND, respectively.

Question 14

NOTE

Hypomagnesemia is a prominent feature with Gitelman, but not typical with bartter syndromes. Reasons are not clear but suggested here:

Answer 14

There are apoptotic and/or histologic changes in DCT in patients with Gitelman that could affect DCT Mg2+ reabsorption, but not in patients with Bartter syndrome. These changes are thought to occur later than other electrolyte changes, hence the absence of hypomagnesemia observed in early disease.

Compensatory DCT Mg2+ reabsorption with loop Mg2+ wasting

Question 15

Management of Bartter and Gitelman Syndromes

Answer 15

Potassium and magnesium supplement as needed

Consider renin angiotensin aldosterone inibitors