Gitelman syndrome is an autosomal recessive inheritance pattern characterized by low levels of potassium, low magnesium, and metabolic alkalosis. Gitelman syndrome is caused by a genetic mutation, known as an autosomal recessive inheritance pattern, affecting a type of protein needed to transport these and other electrolytes through the membranes of the kidneys.
It is estimated that Gitelman syndrome occurs in one to 10 in 40,000 people, affecting males and females of all ethnic backgrounds. There is no cure for Gitelman syndrome.
Around 80% of all cases are associated with a specific genetic mutation known as SLC12A3. This anomaly directly affects the something called the sodium-chloride cotransporter (NCCT), whose function is to reabsorb sodium and chloride from fluids in the kidneys. While the SLC12A3 mutation is the predominant cause of Gitelman syndrome, around 180 other mutations have also been implicated.
A secondary effect of the SLC12A3 mutation is the increase in calcium reabsorption in the kidney. While this effect is also linked to the malabsorption of magnesium and potassium, scientists are still not entirely sure how or why this happens.
People with Gitelman syndrome can sometimes experience no symptoms at all. When they do develop, they are more often seen after the age of 6.
The range of symptoms is directly related to low potassium (hypokalemia), low magnesium (hypomagnesemia), low chloride (hypochloremia), and high calcium (hypercalcemia), in association with a low pH level. The most common signs of Gitelman include:
- Generalized weakness
- Muscle cramping
- Excessive urination or urination at night
- Salt cravings
Less commonly, people may experience abdominal pain, vomiting, diarrhea, constipation, or fever. Seizures and facial paresthesia (the loss of sensation in the face) have also been known to occur.
Some adults with Gitelman syndrome may also develop chondrocalcinosis, a form of pseudo-arthritis caused by the formation of calcium crystals in connective tissues. Although people may initially have low or normal blood pressure, hypertension may develop in later life.
Gitelman syndrome is diagnosed based on a physical examination, a review of symptoms, and the results of blood and urine analyses. More common causes of low potassium and metabolic alkalosis are excluded. Surreptitious vomiting or diuretic use might present with similar findings.
Lab results would typically show:
- Low levels of potassium in the blood
- Low levels of magnesium in the blood
- Low levels of calcium in the urine
Gitelman syndrome is often revealed during a routine blood test when abnormally low potassium levels are detected. When this happens, doctors perform additional tests to ascertain if it is Gitelman syndrome, an associated disease known as Bartter syndrome, or other possible diseases.
Lifelong treatment often includes liberal salt intake along with adequate potassium and magnesium replacement as indicated by laboratory monitoring. NSAIDs and agents that block the distal tubule sodium-potassium exchange (like spironolactone) may be helpful in some people but are not tolerated by others. Kidney transplant corrects the abnormality but has only very rarely been used .
Persons diagnosed with Gitelman syndrome, whether symptomatic or not, are counseled on ways to maintain healthy levels of potassium, magnesium, sodium, and chloride. These include dietary changes and the appropriate use of potassium-sparing diuretics to excrete water through urination but retain potassium.