Bartter syndrome is a genetic disorder characterized by hypokalemia, hypochloremia, metabolic alkalosis, and hypercalciuria. It results from defects in sodium, chloride, and potassium transporters in the ascending loop of Henle. There are four main types based on the underlying molecular defects. The neonatal form presents in newborns with severe salt wasting, dehydration, and hypotension. Classic Bartter syndrome presents in older infants and children with muscle cramps, weakness, and growth failure due to chronic hypokalemia. Treatment involves potassium and sodium supplementation and potassium-sparing diuretics. With adequate treatment, long-term prognosis is generally good, though some may have chronic complications

1. 5 months old ,Vaiga

2. BARTTER
SYNDROME
BY
Dr. NIBIN K B

3. Renal tubular disorders
• Conditions with hypokalemia and metabolic alkalosis

4. Congenital
renal tubular
disorders

5. Bartter syndrome
• It is a group of disorder characterized by hypokalemic, hypochloremic,
metabolic alkalosis with hypercalciuria and salt wasting .
• First reported by Bartter in 1962
• AR
• Hyperreninemia,hyperaldosteronism also present
• Blood pressure remains normal
• Urine levels of sodium,chloride and potassium are increased
• Two types : neonatal bartter– before or immediately after birth
• classical bartter --- occur in neonates or infants aged 2 yrs or
• younger

6. Pathophysiology
• Resembles those seen with chronic use of loop diuretics
• Reflect a defect in Na,Cl,K transport in ascending loop of henle
loss of
Na,cl
Volume
contraction
Stimulate
RAAS
Aldosterone increase Na
uptake & K excretion &
exacerbate
hypokalemia,stimulate H+
secretion distally
hypokalemia stimulate PG
synthesis

7. • 4 types based on the underlying molecular defects in the following loop of
henle transporters ,
• Na/K/2Cl transporter (NKCC2,the site of action of furosemide )
• The luminal potassium channel(ROMK)
• Combined chloride channel (CLC-Ka,CLC-Kb)
• Subunit of chloride channels (barttin)--- these cause neonatal barter
syndrome
• Isolated defects in genes that produce a specific basolateral chloride channel
(ClC-Kb ) cause classic barters syndrome

8. • Type 1,2,4 are neonatal forms , i.e, antenatal barter ,also known as
hyperprostagalndin E syndrome
• Type 3 – classical barter syndrome

10. Clinical features of barters syndrome
• In neonatal bartter
• Generally born preterm
• Marked intrauterine polyuria—polyhydramnios
• Polyuria upto 12-50 ml/kg/hr continues postnatally and cause severe
dehydration
• Dysmorphic features include
• Trangular facies,protruding ears ,large eyes with strabismus ,drooping
mouth

12. • Older children have muscle cramps,weakness,secondary to chronic
hypokalemia ,polyuria,polydipsia ,growth failure,chronic
constipation,dizziness
• Bp usually normal,but patients with antenatal form can have severe salt
wasting – dehydration and hypotension
• Renal function typically normal
• Marked hypercalciuria with nephrocalcinosis is consistent with neonatal
form and rare in classic type

13. Diagnosis
• Based on clinical presentation and lab findings
• In neonate / infant – severe hypokalemia(usually <2.5mmol/L)
,hyponatremia,Metabolic alkalosis,hyperaldosteronism, increased
renin,hyperuricemia ,hypercalciuria,nephrocalcinosis will be present often
• Hypomagnesemia present in minority only ( but more common in
gittelman)
• Differential diagnosis
• diuretic abuse
• Chronic vomiting
• Cystic fibrosis urinary Cl is low in these but increased in bartters

14. Treatment
• Primary aim to correct hypokalemia,volume deficit,maintain nutritional
status
• KCl given 1-3 mEq /kg/day
• Additionally K sparing diuretics spironolactone 10-15 mg/kg/day or
triamterene 10mg/kg/day may be used
• Most effective drugs are PG synthetase inhibitors ,mainly indomethacin 2-
4 mg/kg/day,but look for s/e nausea,vomiting,abdominal pain ,peptic
ulcer ,renal,hepatic toxicity
• Infants and young children require high Na diet,and at times Na
supplementation .
• If needed supplement Mg also .

15. prognosis
• Long term prognosis with adequate treatment is generally good
• In a minority, chronic hypokalemia,nephrocalcinosis,can occur
• Chronic indomethacin therapy can lead to chronic interstitial nephritis
and chronic renal failure

16. GITTELMAN SYNDROME
• A/k/a bartter syndrome variant
• AR
• Pathophysiology
• Due to defective functioning of thiazide sensitive NaCl co transporter
(NCCT)of distal convoluted tubule due to inactivating mutations in the gene
SLC12A3,locus 16q13
• Hypokalemic , hypochloremic metabolic alkalosis with distinct features of
hypocalciuria and hypomagnesemia
• Biochemical features resemble chronic use of thiazide diuretics

17. Clinical features
• Present in late childhood or early adulthood
• Symptoms similar to older children with bartter
• Recurrent muscle cramps,spasms,due to low serum Mg levels
• Nocturia,polyuria,occasional hypotension
• Biochemically : hypokalemia
• metabolic alkalosis
• Hypomagnesemia
• Urine Ca level very low
Urine Mg level low
Renin& aldosterone levels normal
Prostaglandin E not elevated
Growth failure is less prominent compared to bartters

18. Diagnosis
• When an adolescent or adult presenting with hypokalemia , hypochloremia,
metabolic alkalosis, hypomagnesemia, hypocalciuria
• Treatment
• K & Mg supplementation
• Na supplementation or PG inhibitors are not needed
• Prognosis
• Excellent long term outcome with preserved renal function

20. Other inherited tubular transport abnormalities
• Cystinuria
• AR
• Characterised by recurrent stool formation
• Due to defective high affinity transporter for L cystine and dibasic
aminoacids present in proximal tubule
• Dent disease
• X linked proximal tubulopathy with low molecular weight
proteinuria,hypercalciuria,and other features of Fanconi syndrome like
glycosuria,aminoaciduria,phosphaturia

21. • Gordon syndrome (familial hyperkalemic hypertension)
• Occur in DCT
• Due to gain of function mutation of WNK 1 and loss of function mutation of
WNK 4 ,both serine threonine kinases ,lead to excessive NCCT mediated
salt reabsorption
• Clinical picture is of pseudohypoaldosteronism type 2 i.e,
• Volume expansion with HTN
• Hyperkalemia
• Hyperchloremic metabolic acidosis
• Hypercalciuria
• Treatment : thiazide diuretics

22. Liddle syndrome
• Occur in collecting duct
• Gain of function mutation of gene encoding ENaC
• Clinical feature : HTN
• They have constitutive Na uptake in collecting duct with hypokalemia &
supressed aldosterone
• Treatment: amiloride like potassium sparing diuretics
•Pseudohypoaldosteronism
• Due to loss of function mutation of ENaC
• Severe Na wasting ,hyperkalemia &distal RTA (type1V)

23. Renal hypouricemia
• Defect in SLC22A12 gene
• Clinical features: low serum uric acid levels
• Exercise induced acute renal failure ( loin pain,nausea,vomiting after
exercise)
• Elevated urine uric acid levels
• Treatment : of acute renal failure and reducing the intensity of exercise

24. Thank you