Bartter syndrome and Gitelman syndrome are rare, inherited kidney disorders that disrupt the body’s ability to maintain a proper balance of salts and electrolytes. These conditions stem from genetic defects that impair kidney function, leading to various electrolyte imbalances. While both are salt-wasting tubulopathies, distinct characteristics set them apart in presentation and physiological effects.
Bartter Syndrome
Bartter syndrome is a rare genetic disorder caused by defects in the kidney’s thick ascending limb of the loop of Henle. It results from mutations in genes such as NKCC2, ROMK, ClC-Kb, or Barttin, which encode proteins responsible for ion transport. These genetic changes impair the reabsorption of sodium, potassium, and chloride, leading to their excessive loss in urine.
Individuals with Bartter syndrome often exhibit polyuria (excessive urination) and polydipsia (excessive thirst). Growth retardation is common, and severe cases can involve life-threatening dehydration. Characteristic electrolyte abnormalities include hypokalemia (low blood potassium), metabolic alkalosis (increased blood pH), and hypochloremia (low blood chloride). Patients also have hypercalciuria (excessive calcium excretion in the urine) and typically maintain normal to low blood pressure.
Gitelman Syndrome
Gitelman syndrome is an inherited kidney disorder caused by mutations in the SLC12A3 gene. This gene encodes the thiazide-sensitive sodium-chloride cotransporter (NCC), a protein found in the distal convoluted tubule of the kidney. A defect in this transporter impairs the reabsorption of sodium and chloride, mimicking thiazide diuretics.
Symptoms of Gitelman syndrome appear later in life, often during adolescence or adulthood, and are generally milder than Bartter syndrome. Common presentations include muscle weakness, fatigue, and cramps. Some individuals may also experience paresthesias (tingling or numbness) or tetany (muscle spasms). The electrolyte profile includes hypokalemia, metabolic alkalosis, and notably, hypomagnesemia (low blood magnesium). Hypocalciuria (low calcium excretion in urine) is a distinguishing feature, and patients usually have normal to low blood pressure.
Distinguishing Features
Age of onset is a notable difference. Bartter syndrome typically manifests earlier, often prenatally with polyhydramnios or during infancy and early childhood. Gitelman syndrome, in contrast, usually presents later, in late childhood or adulthood, with milder symptoms.
Symptom severity also varies, with Bartter syndrome generally more severe due to its earlier onset and profound electrolyte disturbances. Both syndromes share hypokalemia and metabolic alkalosis, but their distinct electrolyte profiles are key. Bartter syndrome features hypercalciuria (high urinary calcium) and normal to low magnesium levels, while Gitelman syndrome presents with hypocalciuria (low urinary calcium) and significant hypomagnesemia.
The specific kidney defect location further distinguishes them. Bartter syndrome involves the thick ascending limb of the loop of Henle, affecting various ion transporters and leading to a furosemide-like effect. Gitelman syndrome is characterized by a defect in the thiazide-sensitive sodium-chloride cotransporter in the distal convoluted tubule. Both conditions typically maintain normal or low blood pressure, despite increased renin and aldosterone levels, reflecting the body’s compensation for salt loss.
Diagnosis and Management Approaches
Diagnosis involves clinical evaluation and laboratory tests. Blood and urine tests assess electrolyte levels (potassium, chloride, magnesium, calcium) and acid-base balance. A 24-hour urine collection for calcium excretion helps differentiate: high levels suggest Bartter syndrome, low levels indicate Gitelman syndrome. Genetic testing provides a definitive diagnosis by identifying specific gene mutations.
Management focuses on lifelong symptomatic treatment and correcting electrolyte imbalances. Electrolyte supplementation, particularly potassium and magnesium, is a primary treatment. Medications reduce renal salt loss; for Bartter syndrome, non-steroidal anti-inflammatory drugs (NSAIDs) like indomethacin may reduce prostaglandin production, which contributes to salt wasting. For Gitelman syndrome, potassium-sparing diuretics help retain potassium. Dietary adjustments, such as increased salt intake for Bartter syndrome, are also part of the individualized management plan.