OVERVIEW
Gitelman syndrome, also known as familial hypokalemia and hypomagnesemia, is an autosomal recessive disorder of primary renal salt-loss due to impaired reabsorption of sodium and chloride ions in the distal tubules of the kidney. Clinical manifestations include hypokalemia, hypochloremic alkalosis, hypomagnesemia, low urinary calcium and normal or low blood pressure and activated renin-angiotensin-aldosterone system symptoms. The prevalence of this syndrome is difficult to estimate due to its insidious onset and late recognition of the disease.
Etiology
The syndrome is an autosomal recessive disorder caused by mutations in the SLC12A3 gene located on chromosome 16q13, which encodes the sodium-chloride cotransporter (NCCT), a thiazide-diuretic-sensitive ion channel.NCC proteins are important for renal reabsorption, and the mutations in the SLC12A3 gene cause abnormal expression of NCC proteins, leading to the development of renal symptoms. Abnormal expression of NCC protein, causing increased renal excretion of sodium and potassium, leading to Gitelman syndrome.
Symptoms
Symptoms are usually insidious, mild, and late in life, with onset in adolescence or adulthood. Clinical symptoms are lacking in infancy and early childhood, and most are detected in adulthood as a result of routine blood tests. Patients tend to have symptoms related to low blood potassium and low blood magnesium, such as muscle weakness, fatigue, weakness, increased nocturia, salt craving, thirst, excessive drinking, vomiting, constipation, sensory abnormalities, numbness of the limbs, twitching or convulsions of the hands and feet, and fainting. A few patients may have cardiac arrhythmia, palpitation, fainting or even sudden death.
Examination
1. Laboratory examination
(1) Blood electrolyte measurement
Blood electrolyte measurement can clarify the concentration of potassium, magnesium, sodium, calcium and other ions in the blood, and a decrease in the concentration of potassium and magnesium ions in the blood is found to be helpful for diagnosis.
(2) Urine calcium/creatinine measurement
Urinary calcium/creatinine <0.1 can be found.
(3) Hormone Measurement
Hormone measurement is mainly to measure the concentration of plasma renin, angiotensin, aldosterone and other hormones, and elevated concentrations of these hormones can be found.
(4) Genetic testing
Genetic testing is the main basis for definitive diagnosis, and can detect SLC12A3 gene defects.
2. Electrocardiogram
Electrocardiogram can detect arrhythmia, which can help timely treatment, and some patients have prolonged QT interval on electrocardiogram.
Diagnosis
Diagnosis is mainly based on patients’ clinical manifestations and genetic testing. Patients with symptoms such as muscle weakness, fatigue, malaise, increased nocturia, etc., can be initially diagnosed if they also have uncorrectable hypokalemia (<3.5 mmol/L), hypocalcemia (24-h urine calcium-to-creatinine ratio <0.1) and/or hypomagnesium (<0.65 mmol/L) accompanied by a normal or low blood pressure; a definitive diagnosis can be made if genetic testing reveals a defect in the SLC12A3 gene. Other laboratory markers that may help in the diagnosis include elevated plasma renin, angiotensin, and aldosterone levels, and hypochloremic alkalosis.
Differential Diagnosis
Gitelman’s syndrome needs to be differentiated from Bartter’s syndrome, which usually develops at an early age, after birth or before school age, and is characterized by severe thirst, polydipsia, polyuria, and dehydration, and even developmental disorders or delays. Laboratory tests mostly show hypercalcemia. Renal stone formation may be seen on renal ultrasonography. Genetic testing is performed when necessary.
Treatment
Currently, replacement therapy is the mainstay, i.e., replenishing the lost excess ions of potassium, magnesium, and calcium, such as oral treatment with potassium chloride, potassium magnesium aspartate, and magnesium chloride. The non-selective aldosterone receptor antagonist spironolactone is also commonly used in treatment to reduce renal potassium excretion and loss, but side effects such as gynecomastia and female menstrual disorders can occur at higher doses. In addition, as a renal salt-losing disease, replacement of water and salt loss is essential to prevent volume loss and renal hypoperfusion in patients, but individualized treatment is required.
Prognosis.
Relying on regular monitoring, follow-up and lifelong treatment, most patients have a favorable prognosis, but patients are at a higher risk of developing cardiac arrhythmias, diabetes mellitus, and chronic renal failure.
Care
Adjust diet, choose foods rich in salt and rich in potassium and magnesium.
Prevention
Gitelman syndrome is an autosomal recessive disorder, and genetic counseling can be done before having children if there is a more definite family history.