Gitelman Syndrome

Inherited renal tubular defect resulting in urinary loss of magnesium, sodium, potassium, and chloride with otherwise normal kidneys.

Primary Renotubular Hypomagnesemia-Hypokalemia with Hypocalciuria.

Autosomal recessive; caused by mutation in the thiazide-sensitive sodium-chloride cotransporter gene (SLC12A3 gene). More than 100 different mutations distributed throughout the whole protein have been reported. Gene locus is 16q13.

Alteration of the thiazide-sensitive sodium chloride transporter impairs sodium and chloride reabsorption and stimulates renin and aldosterone secretion, resulting in hypokalemia and metabolic alkalosis. Reasons for renal magnesium wastingare unknown.

Made by biochemical changes (alkalosis, hypokalemia, hypomagnesemia, hypocalciuria). Although some features overlap with Bartter syndrome, in contrast to Bartter syndrome, Gitelman syndrome patients present later in life with hypomagnesemia, high fractional excretion of magnesium, and low calcium excretion, but no overt hypovolemia.

Late childhood presentation with hypokalemic metabolic alkalosis and hypomagnesemia. Either asymptomatic or occasional mild episodes of muscle weakness. Symptoms are precipitated by nonspecific illness and may consist of tetany. Patients are neither polyuric nor polydipsic, but they have hypocalciuria, renal magnesium wasting, and absence of nephrocalcinosis. Chronic dermatitis, skeletal problems with growth retardation (as a consequence of rickets), and chondrocalcinosis; rarely rhabdomyolysis (secondary to severe hypokalemia) can be observed in some patients. Long-term prognosis is rather good, especially when potassium losses are corrected. Treatmentwith oral magnesium corrects the magnesium deficit but not themetabolic alkalosis. The relationship of these skeletal abnormalities to magnesium wasting and hypomagnesemia is not clear.

Obtain history of frequency and severity of tetany and muscle weakness as an indicator of disease severity. Obtain electrolyte levels (potassium, magnesium, calcium) and arterial blood gas analysis. Correct electrolyte abnormalities preoperatively.

The catecholamine stress response associated with direct laryngoscopy and tracheal intubation further exacerbates hypokalemia (intracellular entry). The arrhythmogenic potential of hypokalemia is thought to result from electrical inhomogeneity, alterations in conduction, changes in automaticity, and disturbances in sodium pump kinetics. Hypomagnesemia favors atrial dysrhythmias. Use of a nerve stimulator is mandatory if general anesthesia with muscle relaxants is considered. Postanesthetic care should be in a high-dependency area for 24 to 48 hours or until the patient is stable with normal potassium and magnesium levels. Should cardiac dysrhythmias occur, determination of serum potassium, calcium, and magnesium concentrations are essential in guiding the therapy.

Muscle relaxants (preferably atracurium or cis-atracurium) can be used (under the monitoring of peripheral nerve stimulator). Use of catecholamines and other vasoactive drugs may exacerbate preexisting hypokalemia because of the intracellular shift of potassium. Careful administration of glucose-based intravenous solution may contribute to exaggeration of the hypokalemia.

Bartter Syndrome: Family of disorders characterized by hypokalemic, hypochloremic, hypomagnesemic variants with hypocalciuria, metabolic alkalosis, and normotensive hyperreninemic hyperaldosteronism linked to the gene encoding the thiazide-sensitive Na/Cl-cotransporter (TSC). The responsible gene here is located on chromosome 1p 36.

Gullner Syndrome: Findings differ from those of Bartter syndrome in which hyperaldosteronism and juxtaglomerular hyperplasia are important features and sodium conservation occurs. It is associated with hyperreninemia, high urinary prostaglandin E2, normal blood pressure, and resistance of blood pressure to the pressor effect of angiotensin II. Hypokalemia is corrected by magnesium repletion. Abnormal magnesium metabolism may be responsible for the hypokalemia in this syndrome. Magnesium treatment does not affect renin levels but causes an increase in plasma aldosterone concentration in both the supine and upright positions.

Liddle Syndrome: Autosomal dominant disorder characterized by early, and frequently severe, hypertension associated with hypokalemic metabolic alkalosis, low plasma renin activity, and suppressed aldosterone secretion, another disorder with hypokalemia. It is differentiated from the Gitelman syndrome, Gullner syndrome, and Bartter syndrome by the presence of hypertension.

De Toni Debré Fanconi Syndrome: Rare acquired or inherited condition involving a generalized transport defect in the proximal tubules with renal losses of glucose, phosphate, calcium, uric acid, amino acids, and bicarbonates leading to short stature, osteomalacia, and renal failure.

Periodic Paralysis (PP): Congenital abnormality in membrane electrolyte conductance leading to episodic muscle weakness.

Lightwood Syndrome: Nonhereditary form of primary tubular acidosis presenting with hypercalcemia, hypercalciuria, and nephrocalcinosis.

Albright-Butler Syndrome: Patients present with renal tubular acidosis, nephrocalcinosis, and renal failure. Hypokalemia with muscle weakness and periodic paralysis is frequent. Polyuria, vomiting, and dehydration lead to fluid and electrolyte imbalances.

Adenosine Deaminase Deficiency: Heterogeneous systemic disorder caused by the deficiency of adenosine deaminase resulting primarily in severe combined (cellular and humoral) immunodeficiency but also systemic abnormalities.

Lowe Syndrome: Genetically transmitted polymalformative syndrome characterized by the association of ocular problems with renal dysfunction and mental retardation.

Phosphoenolpyruvate Carboxykinase Deficiency: Congenital metabolic disease leading to a defect in gluconeogenesis.

Propionic Acidemia: Inborn error of metabolism affecting the mitochondrial catabolism of valine and isoleucine that, left untreated, results in ketoacidosis, lethargy, coma, and finally death.

Pyruvate Carboxylase Deficiency: Mitochondrial disease impairing synthetic pathways, leading to hypoglycemia and severe lactic acidosis.

Tyrosinemia: Elevated blood tyrosine levels are present in several clinical entities. The term tyrosinemia is used to describe several syndromes. In general, the association of liver and renal failure, marked edema, epistaxis, and distinctive cabbage-like odor are characteristic of the disease.