Gitelman syndrome is a rare, inherited kidney disorder that alters how the body processes salt and other electrolytes. It is a type of salt-wasting nephropathy, meaning the kidneys excrete too much sodium into the urine, which leads to a cascade of electrolyte imbalances. Although it is a lifelong diagnosis, the symptoms are manageable with consistent medical care. The disorder affects approximately 1 in 40,000 people and is identified during adolescence or adulthood.
Genetic Causes and Pathophysiology
Gitelman syndrome is caused by mutations in the SLC12A3 gene. This condition follows an autosomal recessive inheritance pattern, which means an individual must inherit two copies of the mutated gene—one from each parent—to develop the syndrome. The parents are carriers who have one copy of the mutation but do not show symptoms themselves.
The SLC12A3 gene holds the instructions for building a protein called the thiazide-sensitive sodium-chloride cotransporter (NCC). This protein is located in the walls of a specific segment of the kidney’s filtering units, the distal convoluted tubules. The function of the NCC protein is to reabsorb sodium and chloride from the fluid that is being processed into urine, returning these electrolytes to the bloodstream.
When the SLC12A3 gene is mutated, the resulting NCC protein is defective and cannot perform its transport function correctly. This impairment leads to a significant loss of sodium and chloride in the urine. The excessive salt loss triggers a series of downstream effects, including the increased excretion of potassium and magnesium, leading to low levels of these electrolytes in the blood.
Signs and Symptoms
The clinical presentation of Gitelman syndrome varies, with some people remaining asymptomatic while others experience noticeable symptoms. Symptoms often do not appear until late childhood, adolescence, or even adulthood. A common complaint is a distinct craving for salty foods, which is the body’s response to the continuous loss of sodium through the urine.
Many symptoms are directly related to the low levels of potassium and magnesium in the blood, known as hypokalemia and hypomagnesemia. These electrolyte shortages can cause persistent fatigue, muscle weakness, and painful muscle cramps or spasms. Some individuals may also experience dizziness, numbness, or tingling sensations, particularly in the hands, feet, or face.
Low blood pressure, or hypotension, is another common finding, resulting from the body’s reduced salt and water volume. In some cases, gastrointestinal issues such as abdominal pain, nausea, and vomiting can occur. Another related symptom is frequent urination, sometimes including at night, as the kidneys are less able to concentrate urine. Over time, some people may develop a condition called chondrocalcinosis, where calcium crystals build up in the joints, leading to pain and swelling.
Diagnosis Process
If clinical signs suggest a salt-losing kidney disorder, a series of blood and urine tests are performed to measure electrolyte levels. These tests reveal a characteristic pattern of abnormalities that point toward Gitelman syndrome.
The blood test findings include low levels of potassium (hypokalemia) and magnesium (hypomagnesemia). Blood work also shows metabolic alkalosis, which is an elevated blood pH. At the same time, urine tests will show high levels of sodium, chloride, and potassium being excreted, confirming that the kidneys are the source of the electrolyte loss.
A feature that helps differentiate Gitelman syndrome from similar conditions, such as Bartter syndrome, is the level of calcium in the urine. Individuals with Gitelman syndrome have characteristically low urinary calcium excretion, a finding known as hypocalciuria. While this combination of results is often sufficient for a diagnosis, genetic testing can provide a definitive confirmation. This testing identifies disease-causing mutations in both copies of the SLC12A3 gene.
Management and Treatment Strategies
As there is no cure for Gitelman syndrome, treatment is centered on managing symptoms and correcting the underlying electrolyte imbalances through lifelong intervention. The goal is to replenish the minerals that are continuously lost through the urine. This management requires regular monitoring by a nephrologist, a doctor specializing in kidney disorders.
The foundation of treatment is oral supplementation of potassium and magnesium. Patients often require large daily doses to counteract urinary losses, and these supplements may need to be taken in smaller, divided doses throughout the day to minimize side effects like diarrhea, which can be a common issue with magnesium supplements. The specific amounts are tailored to each individual based on regular blood tests.
Dietary adjustments are also a component of the management plan. Patients are advised to consume a diet that is high in both salt and potassium to help offset what is lost by the kidneys. Foods rich in potassium, such as bananas and potatoes, are often encouraged. This dietary approach should only be followed under the guidance of a specialist kidney dietitian to ensure proper balance and monitoring.
In addition to supplements and diet, certain medications may be prescribed. Potassium-sparing diuretics, such as spironolactone or amiloride, can be used to help the body retain potassium. For those who develop joint pain from chondrocalcinosis, nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to reduce discomfort. Treatment plans are adjusted over time based on symptoms and laboratory results.