Gitelman syndrome

Gitelman syndrome

Other Names:Potassium and magnesium depletion; Hypomagnesemia-hypokalemia, primary renotubular, with hypocalciuria; Familial hypokalemia-hypomagnesemia; Gitelman's syndrome

Gitelman syndrome is a kidney disorder that causes an imbalance of charged atoms (ions) in the body, including ions of potassium, magnesium, and calcium.

Onset

The signs and symptoms of Gitelman syndrome usually appear in late childhood or adolescence.

Epidemiology

Gitelman syndrome affects an estimated 1 in 40,000 people worldwide.

Cause

Gitelman syndrome is usually caused by mutations in the SLC12A3 gene. Less often, the condition results from mutations in the CLCNKB gene. The proteins produced from these genes are involved in the kidneys' reabsorption of salt (sodium chloride or NaCl) from urine back into the bloodstream. Mutations in either gene impair the kidneys' ability to reabsorb salt, leading to the loss of excess salt in the urine (salt wasting). Abnormalities of salt transport also affect the reabsorption of other ions, including ions of potassium, magnesium, and calcium. The resulting imbalance of ions in the body underlies the major features of Gitelman syndrome.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

Signs and symptoms of Gitelman syndrome tend to present in adolescents and adults, but occasionally present in infants and young children. Signs and symptoms in children and adults vary, but may include: A preference for salty foods (salt craving)

• Muscle weakness
• Fatigue
• Limited sports performance or endurance
• Episodes of fainting
• Cramps
• Muscle spasms
• Numbness or tingling (such as of the face)
• Growth delay
• Delayed puberty
• Short stature
• Excessive thirst
• Abdominal pain

Adults with Gitelman syndrome may also experience dizziness, vertigo, excessive amount of urine, urinating more at night, heart palpitations, joint pain, and vision problems. Other possible symptoms include low blood pressure, a painful joint condition called, chondrocalcinosis, prolonged QT interval (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death), episodes of elevated body temperature, vomiting, constipation, bed wetting, and paralysis. Additional rare symptoms have been described in single cases.

Diagnosis

A diagnosis of Gitelman syndrome may be suspected in children and adults with characteristic symptoms. A number of blood and urine tests aid in the diagnosis of Gitelman syndrome, such as:

• Potassium urine test
• Blood gases
• Blood tests to measure magnesium, aldosterone, and renin
• Urine analysis for sodium, potassium, and calcium

Common blood and urine abnormalities found in Gitelman syndrome, include:

• Low levels of potassium in the blood (hypokalemia)
• Metabolic alkalosis (too much base in the body)
• Low magnesium in the blood (hypomagnesemia)
• Low levels of calcium in the urine (hypocalciuria)

Anorexia, bulimia, chronic diarrhea, vomiting, and long term use of laxatives or diuretics can cause similar signs and symptoms. Before a diagnosis of Gitelman syndrome is made these conditions must be ruled out. A careful review of the patient and family health histories, as well as renal ultrasound findings can be helpful in ruling out other causes.

Genetic testing can confirm a diagnosis of Gitelman syndrome. Tools for finding genetic testing for Gitelman syndrome are available below.

Treatment

The mainstay treatment of Gitelman syndrome involves careful monitoring, high-sodium and potassium diet, and oral potassium and magnesium supplements. Intravenous magnesium and/or potassium may be needed if symptoms are severe. People who have low potassium levels despite supplementation and diet, may benefit from potassium-sparing diuretics, renin angiotensin system blockers, pain medications, and/or nonsteroidal anti-inflammatory drugs (NSAIDs).

The Blanchard A et al., 2017 consensus guideline offers detailed treatment information, including information on drug selection, dosing recommendations, and a listing of drugs that can cause adverse effects in people with Gitelman syndrome.

Lastly, people with Gitelman syndrome should have a thorough heart work-up. People with Gitelman syndrome and a prolonged QT interval should avoid drugs that prolong the QT interval.

Prognosis

The long-term outlook (prognosis) for people with Gitelman syndrome is generally very good. However, the symptoms and severity can vary from person to person. Some people do not develop any symptoms, while others develop chronic issues that can impact their quality of life. Weakness, fatigue and muscle cramping can affect daily activities in some people with Gitelman syndrome. In general, while the underlying condition does not appear to be progressive, complications can arise, especially if care recommendations are not followed.

Progressive renal insufficiency is extremely rare. Renal function is usually maintained despite long-term hypokalemia (low potassium), but progression to chronic renal insufficiency has rarely been reported.

Some people with Gitelman syndrome may be at risk of developing cardiac arrhythmias. Those with severe hypokalemia are more susceptible to cardiac arrhythmias, which can be life-threatening when joined with severe hypomagnesemia (low magnesium) and alkalosis. Therefore, an in-depth cardiac work-up is strongly recommended to identify which people with Gitelman syndrome may be at risk. Competitive sports should be avoided because sudden death can be precipitated by intense physical activity that induces potassium and magnesium loss by sweating.

NIH genetic and rare disease info

• NIH info on Gitelman syndrome

Gitelman syndrome is a rare disease.

Gitelman syndrome Resources
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