Bartter syndrome is a rare, inherited kidney disorder. This condition arises when the kidneys fail to reabsorb salt correctly, leading to excessive loss of potassium, sodium, and chloride in the urine. The resulting electrolyte imbalances can disrupt various bodily functions and impact overall health. It is a lifelong condition requiring ongoing medical attention.
The Underlying Genetic Causes
The kidneys contain millions of tiny filtering units called nephrons, each with a segment known as the thick ascending limb of the loop of Henle. In healthy individuals, this part of the kidney reabsorbs salt (sodium and chloride) and other electrolytes back into the bloodstream. This process relies on specialized proteins, including transporters and channels, that move these ions across cell membranes.
Barter syndrome is caused by genetic mutations that impair the function of these proteins in the thick ascending limb.
Type I results from mutations in the SLC12A1 gene, affecting the Na-K-2Cl cotransporter (NKCC2).
Type II is linked to mutations in the KCNJ1 gene, affecting a potassium channel called ROMK.
Type III is caused by mutations in the CLCNKB gene, affecting a basolateral chloride channel.
Type IV involves mutations in the BSND gene or a combination of CLCNKA and CLCNKB genes, often leading to sensorineural deafness.
A rarer Type V is associated with mutations in the CASR gene, which encodes the calcium-sensing receptor.
Signs and Symptoms
In the Womb and Infancy
Barter syndrome can manifest even before birth, often identified by excessive amniotic fluid (polyhydramnios), typically between 24 and 30 weeks of gestation. This can increase the likelihood of premature birth. After birth, affected infants often display a failure to thrive. They may also experience frequent urination and intense thirst, leading to dehydration. Vomiting and diarrhea are common gastrointestinal issues.
In Childhood and Adulthood
As individuals with Barter syndrome grow, symptoms persist. Older children and adults often report strong cravings for salt, reflecting the body’s ongoing salt loss. Muscle weakness and painful muscle cramps are common due to low blood potassium levels. Frequent urination (polyuria) and excessive thirst (polydipsia) remain prominent, often causing fatigue. In some cases, calcium deposits can form in the kidneys, leading to nephrocalcinosis or kidney stones.
Diagnostic Process
Diagnosing Barter syndrome begins with symptom evaluation and medical history. Laboratory tests identify characteristic electrolyte imbalances in the blood and urine. Blood tests often reveal low potassium (hypokalemia), low chloride, and increased renin and aldosterone. Urine tests show abnormally high concentrations of sodium, potassium, and chloride being excreted.
Initial findings suggest Barter syndrome, but genetic testing provides definitive confirmation. This testing analyzes associated genes (SLC12A1, KCNJ1, CLCNKB, BSND, CASR) to identify the precise genetic mutation and type. Prenatal ultrasound may also suggest Barter syndrome before birth by showing polyhydramnios, supported by elevated chloride in amniotic fluid.
Treatment and Management Strategies
Managing Barter syndrome focuses on correcting electrolyte imbalances and mitigating symptoms. Treatment involves high-dose potassium supplements to replenish lost potassium. Oral salt supplements also compensate for excessive sodium and chloride excretion. Supplements are adjusted based on regular blood electrolyte monitoring.
NSAIDs (e.g., indomethacin) reduce prostaglandin production, which contributes to salt and water loss. This decreases urine output and conserves potassium. Other medications, such as ACE inhibitors or potassium-sparing diuretics (e.g., spironolactone), may block hormonal pathways that contribute to potassium wasting and stabilize electrolyte levels. Maintaining adequate hydration and following a diet high in salt and potassium are also important.
Living with Barter Syndrome
Barter syndrome is a lifelong condition requiring continuous medical care and monitoring. Individuals with the syndrome require regular follow-up appointments with a nephrologist to assess kidney function and manage electrolyte levels. Long-term management aims to prevent severe dehydration, support normal growth, and protect kidney function. Consistent adherence to treatment minimizes the disorder’s impact on daily life.
With proper management, many individuals can lead full lives, though potential complications are monitored. Complications can include chronic kidney disease, especially in Types I and IV. Sensorineural hearing loss is another potential complication in certain types, like Type IV, requiring monitoring and intervention. Early recognition and consistent treatment improve the long-term outlook.