OVERVIEW
Gitelman syndrome (GS), also known as Gitelman syndrome, is an autosomal recessive renal tubular disorder with hypokalemia and metabolic alkalosis as the main clinical manifestations, often accompanied by hypocalcemia and hypomagnesemia. It is mostly asymptomatic in infancy, and is mostly detected during routine examination in adulthood or when hypokalemia and alkalosis are present. Treatment requires the combined application of potassium-preserving diuretics.
Etiology
Gitelman syndrome is caused by a loss-of-function mutation in SLCl2A3, the gene encoding the thiazide diuretic-sensitive sodium-chloride cotransporter (NCCT) protein located in the distal tubules of the kidney, leading to structural and/or functional abnormalities of the NCCT, which causes impaired sodium-chloride reabsorption in the distal tubules of the kidneys and results in hypovolemia, activation of the renin-angiotensin-aldosterone system (RAAS), hypokalemia and metabolism. This leads to hypovolemia, activation of the renin-angiotensin-aldosterone system (RAAS), hypokalemia, and metabolic alkalosis.
Symptoms
Typical clinical manifestations are “five lows and one high” and metabolic alkalosis, i.e., hypokalemia, hypomagnesemia, hypochlorhydria, hypocalcemia, low blood pressure and increased RAAS activity. Most patients develop the disease in adolescence or adulthood, and about 1/3 of patients may have a clear family history. The common clinical symptoms are non-specific and related to electrolyte disorders and RAAS activation.
1. Systemic symptoms
Limb weakness, fatigue, decreased exercise tolerance and thirst.
2. Cardiovascular system
Normal or low blood pressure, palpitations, prolonged QT interval, ventricular arrhythmia.
3. Digestive system
Episodes of abdominal pain, constipation, vomiting.
4. Urinary system
Polyuria, nocturia, enuresis, proteinuria, hypokalemic nephropathy.
5. Neuromuscular system
Dizziness, vertigo, ataxia, pseudotumor cerebri, limb numbness, sensory abnormalities, muscle spasm, convulsions, rhabdomyolysis.
6. Bone and joint system
Arthralgia, cartilage calcium deposits.
7. Growth and development
Developmental stagnation, growth retardation, delayed puberty. It should be pointed out that most patients have normal or mildly elevated quantitative urine protein, usually small and medium molecular proteins, which may be related to renal tubular injury caused by long-term low potassium, and most patients have normal renal function, so there is no need for renal puncture biopsy. However, if the patient has a large amount of proteinuria, unexplained impaired renal function, etc., renal puncture biopsy is needed to clarify whether there is a combination of glomerulopathy or other renal diseases.
Tests
1. Biochemical examination
Due to the lack of specificity of the patient’s symptoms, clinical diagnosis is more dependent on laboratory tests, especially low blood magnesium and low urinary calcium are of great value to the diagnosis. Laboratory findings that support the diagnosis of Gitleman syndrome mainly include: (1) hypokalemia and renal potassium loss; (2) metabolic alkalosis; (3) hypomagnesemia and increased renal excretion of magnesium; (4) low urinary calcium; (5) activation of the RAAS system; and (6) a fractional excretion of chloride ions (FECI) >0.5%.
2. Imaging examination
Renal ultrasonography is normal, and there are usually no calcium deposits or developmental abnormalities.
3. Genetic testing
All patients should undergo a family lineage survey, and genetic testing is recommended in qualified institutions to confirm the diagnosis. Mutations at the T60M and D486N loci are more common in our patients and can be used as a reference for genetic screening.
Diagnosis
Typical Gitleman syndrome patients can be clinically diagnosed by clinical manifestations and laboratory tests, but the final diagnosis depends on genetic testing.
Treatment
1. Potassium and magnesium supplementation
Oral or intravenous potassium and/or magnesium supplementation is the mainstay of treatment and needs to be individualized and lifelong. If the patient has low blood magnesium, magnesium supplementation should be the first step in helping to maintain normal potassium levels while avoiding complications such as convulsions. It is recommended to maintain blood potassium and magnesium levels at least 3.0 mmol/L and 0.6 mmol/L respectively.
Encourage patients to eat foods rich in potassium ions. Potassium chloride can be used as the drug for potassium supplementation, avoiding oral intake on an empty stomach to minimize gastrointestinal stimulation, and the dose can be gradually increased until a suitable maintenance level is reached. Oral administration is preferred for magnesium supplementation, and attention should be paid to the bioavailability of different preparations. When patients have serious complications or cannot tolerate oral magnesium supplementation, intravenous magnesium supplementation is required.
2. Other drugs
When the patient has persistent hypokalemia with related symptoms, and the effect of potassium supplementation is not good or the side effects cannot be tolerated, the use of potassium-preserving diuretics can be considered.
3. Treatment of chondrocalcinosis
This disease is relatively rare, usually need to pay attention to magnesium supplementation for prevention.