Gitelman Syndrome

What ist Gitelman Syndrome?

Gitelman syndrome, also known as familial hypokalemia-hypomagnesemia, is a rare genetic disorder that affects the kidneys' ability to reabsorb certain minerals, particularly potassium and magnesium. It is characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesemia and low urinary calcium excretion. The prevalence is estimated at approximately 1:40,000 and accordingly, the prevalence of heterozygotes is approximately 1% in Caucasian populations, making it one of the most frequent inherited renal tubular disorders.

It is an autosomal recessive disorder, meaning that an individual needs to inherit two copies of the mutated gene (one from each parent) to develop the condition. The syndrome is caused by mutations in the SLC12A3 gene, which is responsible for encoding a protein called the thiazide-sensitive sodium-chloride cotransporter (NCC) in the kidneys. The NCC is essential for reabsorbing sodium and chloride, as well as indirectly influencing the reabsorption of potassium and magnesium in the distal convoluted tubules of the kidneys.

In Gitelman syndrome, the defective NCC protein leads to excessive loss of sodium, chloride, potassium, and magnesium in the urine, resulting in hypokalemia (low potassium levels) and hypomagnesemia (low magnesium levels).

Gitelman Syndrome Symptoms:

 

  • Fatigue and weakness
  • Muscle cramps and spasms
  • Increased thirst and urination
  • Nausea and vomiting
  • Abdominal pain
  • Dizziness and fainting (due to low potassium levels affecting heart function)
  • Tetany (in severe cases).

In the majority of cases, symptoms do not appear before the age of six years and the disease is usually diagnosed during adolescence or adulthood. Transient periods of muscle weakness and tetany, sometimes accompanied by abdominal pain, vomiting and fever are often seen in GS patients. Paresthesias, especially in the face, could frequently occur. Remarkably, some patients are completely asymptomatic except for the appearance at adult age of chondrocalcinosis that causes swelling, local heat, and tenderness over the affected joints. Blood pressure is lower than that in the general population.

Diagnosis:

The diagnosis of GS involves blood and urine tests to assess the levels of potassium, magnesium, and other electrolytes. Genetic testing can confirm the presence of mutations in the SLC12A3 gene. Antenatal diagnosis for GS is technically feasible but not advised because of the good prognosis in most patients.

It's important to note that GS is a chronic condition, but with appropriate medical care and adherence to the prescribed treatment plan, individuals with the syndrome can lead relatively normal and healthy lives. In general, the long-term prognosis of GS is excellent.

Gitelman Syndrome Treatment:

Treatment of GS typically involves managing the electrolyte imbalances. Lifelong supplementation of magnesium (magnesium-oxide and magnesium-sulfate), in some cases, medications that help spare potassium and magnesium in the kidneys (such as potassium-sparing diuretics) is recommended. Regular monitoring of electrolyte levels and kidney function is essential to prevent complications and ensure proper management of the condition. Cardiac work-up should be offered to screen for risk factors of cardiac arrhythmias. All GS patients are encouraged to maintain a high-sodium and high potassium diet.

Experts Recommendations:


Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.  

Kidney Int 2017; 91:24-33

Core Recommendations:

  1. Clinical diagnosis should be confirmed by genetic testing
  2. Genetic counseling should be offered
  3. Management includes liberal salt intake, as well as Mg and K supplements
  4. Limited evidence for the use of K-sparing diuretics. If done, concomitant salt supplementation should be considered
  5. Subnormal levels for plasma K and Mg levels can be accepted and concentrations of 3.0 mmol/l and 0.6 mmol/l for K and Mg, respectively, should be targeted, but may not be realistic in some patients with severe electrolyte wasting

Comments by evaluators:

This document is not a guideline, but a consensus expert opinion to provide guidance for clinical practice.