Bartter syndrome

Overview

Bartter syndrome is a rare group of inherited renal tubular disorders characterized by an inability of the kidneys to reabsorb sodium, leading to an imbalance of electrolytes. This results in excessive loss of potassium, chloride, and sodium in the urine. The syndrome is named after Dr. Frederic Bartter, who first described it in the 1960s. It primarily affects the function of the thick ascending limb of the loop of Henle in the kidney and manifests with symptoms such as growth retardation, muscle weakness, and metabolic alkalosis. Bartter syndrome is classified into several types based on the specific genetic mutation and severity of symptoms.

Causes

Bartter syndrome is caused by mutations in genes that affect the transport of electrolytes in the kidney's nephron, particularly in the loop of Henle. These genetic mutations disrupt sodium, potassium, and chloride reabsorption.Key causes include:

• Mutations in genes such as SLC12A1, KCNJ1, CLCNKB, BSND, or MAGED2

• Autosomal recessive inheritance – both parents must carry a copy of the defective gene

• Type I–IV Bartter syndrome – classified based on the affected gene and clinical severity

• Type V (transient antenatal form) – typically seen in male infants and caused by MAGED2 mutations

Symptoms

Symptoms of Bartter syndrome can vary depending on the type and severity but typically include signs of fluid and electrolyte imbalance:

• Polyuria and polydipsia (frequent urination and excessive thirst)

• Muscle weakness and cramping due to low potassium levels

• Constipation

• Growth retardation and failure to thrive in children

• Dehydration and low blood pressure

• Metabolic alkalosis – a condition where blood pH becomes too alkaline

• Salt craving

• Hearing loss in some subtypes (particularly Type IV)

Diagnosis

Diagnosis is based on clinical symptoms, laboratory findings, and genetic testing:

• Blood tests – showing low potassium, low chloride, normal or low sodium, and elevated bicarbonate

• Urine tests – revealing high urinary potassium and chloride levels

• Plasma renin and aldosterone levels – typically elevated due to volume depletion

• Normal or low blood pressure – distinguishes it from conditions like hyperaldosteronism

• Genetic testing – confirms the subtype by identifying the causative mutation

Treatment

There is no cure for Bartter syndrome, but treatment aims to correct electrolyte imbalances and manage symptoms:

• Potassium and magnesium supplements to restore electrolyte balance

• Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin – to reduce prostaglandin levels and improve electrolyte reabsorption

• Spironolactone or amiloride – potassium-sparing diuretics to minimize potassium loss

• High-sodium diet in some cases to counter salt wasting

• Regular monitoring of electrolytes and kidney function

• Growth hormone therapy – in cases with severe growth delay

Prognosis

The prognosis of Bartter syndrome varies based on the type and the effectiveness of treatment:

• Most individuals can lead a relatively normal life with early diagnosis and proper electrolyte management

• Growth and development may be delayed but can improve with consistent treatment

• Chronic kidney disease may develop in some patients with severe or long-standing forms

• Prognosis is more favorable in classic and milder forms compared to antenatal types