Gitelman syndrome Detailed Information

Gitelman syndrome (GS), also referred to as familial hypokalemia-hypomagnesemia and characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesemia and low urinary calcium excretion. It causes the kidneys to pass sodium, magnesium, chloride, and potassium into the urine, rather than allowing it to be resorbed into the bloodstream. This syndrome does not cause kidney failure nor does it cause the kidneys to function abnormally. The kidneys are normal. The problem is the reabsorption of important electrolytes and minerals.

 Gitelman's syndrome is linked to inactivating mutations in the SLC12A3 gene resulting in a loss of function of the encoded thiazide-sensitive sodium-chloride co-transporter (NCCT). This cell membrane protein participates in the control of ion homeostasis at the distal convoluted tubule portion of the nephron. Gitelman's syndrome is an autosomal recessive disorder: one defective gene has to be inherited from each parent.

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. The majority of symptoms that these patients have are from the low Magnesium and Potassium levels. 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, frequently occur. Joint pain secondary to chondrocalcinosis has been described in this subset of patients and attributed to the hypomagnesemia. Carriers of Gitelman's syndrome-linked mutations are often asymptomatic while some complain of mild muscular cramps or weakness expressed as fatigue or irritability. Most asymptomatic patients with GS remain untreated but it can be treated by drugs that antagonize the activity of aldosterone or block the sodium channel ENaC in the collecting duct. Amiloride should be started with caution in order to avoid hypotension.