Frederic C. Bartter

First discovered in 1962 by Frederic Bartter. Bartter described this syndrome in two African-American patients: a 5 year old boy and a 25 year old man with a long history of slow growth, weakness and fatigue. On high sodium diets, both patients had normal blood pressure and high urinary aldosterone excretion, resulting in metabolic alkalosis.

NORMAL

Pathophysiology

Defects in the sodium-chloride potassium-chloride cotransporter or potassium channel affect the transport of sodium, potassium, and chloride in the thick ascending limb of the loop of Henle.Leads to delivery of large volumes of urine with a high content of these ions to the distal segments of the renal tubule, where only some sodium is reabsorbed and potassium is secreted.

BARTTER SYNDROME • Decrease reapsortion of Na > Increased excretion of Na in the urine.

• Increase secretion of K and Cl in the urine

Profound hypokalemia (1.5-2.5 mEq/L). Increased urinary excretion of potassium and prostaglandins. Normal blood pressure despite elevated plasma renin and aldosterone levels.   Hypochloremic (Low chloride) metabolic alkalosis. A relative vascular resistance to the pressor effects of exogenous angiotensin II Hyperplasia of the juxtaglomerular apparatus

FEATURES ASSOCIATED WITH BS

Frequency In the USThere are both familial and sporadic forms of Bartter's and Gitelman's syndromes. The prevalence of this disorder is not precisely known

Bartter syndrome genotype-phenotype correlations

Genetic Type Defective Gene Clinical Type

Bartter type I NKCC2 Neonatal

Bartter type II ROMK Neonatal

Bartter type III CLCNKB Classic

Bartter type IV BSND Neonatal with deafness

Bartter type V CLCNKB and CLCNKA Neonatal with deafness

Gitelman syndrome NCCT Gitelman syndrome

Tetany, muscle spasms, Chvostek's sign and Trousseau's sign may be seen in hypokalemia, hypocalcemia, and hypomagnesemia patients. In the older literature rickets was also occasionally reported.

In 1997, Madrigal described a type of this syndrome in Costa Rica in sixteen of the twenty patients with a "peculiar facies, distinguished by a triangularly shaped face, large eyes, and protruding ears".

Another eight had sensorineural hearing loss determined by audiography. 

Clinical Presentation

SymptomsFatigue Polyuria (rate as high as 12-50 mL/kg/h). Polydipsia NocturiaGeneralized weakness Salt Cravings Dehydration  Mental confusion Vomiting Muscle weakness  Muscle spasms Tetany Failure to thrive Short stature (If untreated)

Physical FindingsPatient is thin and have reduced muscle mass and a triangularly shaped face, which is characterized by a prominent forehead, large eyes, protruding ears, and drooping mouth.Strabismus is frequently present.BP is normal.Bartter syndrome (type IV and V) develop sensorineural deafness, ( is detectable with audiometry).

Lab findingsLow serum potassium levels Low-normal magnesium levels Increased renin Increased aldosterone Metabolic Alkalosis Increased Prostaglandin E2 excretion Normal-high urinary calcium excretion Normal-high urinary Mg excretion Normal-low serum Mg levels (20% have dec.Mg levels) Normal - Low Blood Pressure Increased urinary potassium excretion Increased plasma angiotensin II Renal stones

Differential diagnosisCystic fibrosis Cyclical vomitingCongenital chloride diarrheaDiuretic abuseGitelman syndromeGullner syndrome Familial hypokalemicalkalosis with proximal tubulopathyMineralocorticoid excessPyloric stenosis

TreatmentsThere is no cure for Bartter's syndrome. The treatments consist of supplements to replace what is lost and medications to prevent urinary wasting of potassium and magnesium. In younger children growth hormone may be used to prevent the short stature and prostaglandin inhibitors to decrease the elevated prostaglandin levels. 

Potassium Chloride Supplements Magnesium Supplements Spironolactone Amilioride Triamterene Indomethacin Captopril Growth Hormone

Consultations: Consult a pediatric nephrologist to assist with the initial diagnosis and for periodic outpatient evaluation of growth, development, renal function, serum electrolytes, and response to therapy.

Diet: foods and drinks containing high levels of potassium (eg, tomatoes, bananas, orange juice).

Activity: No restriction on general activity is required, but precautions against dehydration should be taken. Patients should avoid strenuous exercise avoided because of the danger of dehydration and functional cardiac abnormalities secondary to potassium imbalance.

Outpatient Care•Growth, development, renal function, and serum electrolytes should be evaluated periodically, ideally in a pediatric nephrology clinic.• Cases of coexisting growth hormone deficiency that respond to growth hormone therapy with catch-up growth have been reported.

Cardiac arrhythmia and sudden death may result from electrolyte imbalances.Failure to thrive, growth retardation, and developmental delay are common in untreated patients.Chronic hypokalemia results in slow progression to chronic renal insufficiency

Complications

Prognosisearly diagnosis and appropriate treatment may improve growth and neurointellectual development. sustained hypokalemia and hyperreninemia can cause progressive tubulointerstitial nephritis, resulting in end-stage-renal disease. With early treatment of the electrolyte imbalances the prognosis is good.Bone age is appropriate for chronological age, and pubertal and intellectual development are normal with treatment.The disease does not recur in the patient with a transplanted kidney.