Bartter Syndrome and Gitelman Syndrome

Bartter syndrome and the more common Gitelman syndrome result from

In Bartter syndrome, the defect is in the ascending thick limb of the loop of Henle. In Gitelman syndrome, the defect is in the distal tubule.

In both syndromes, the impairment of sodium chloride reabsorption causes mild volume depletion, which leads to increases in renin and aldosterone release, resulting in potassium and hydrogen losses. In Bartter syndrome, there is increased prostaglandin secretion as well as a urinary concentrating defect due to impaired generation of the medullary concentration gradient. In Gitelman syndrome, hypomagnesemia and a low urinary calcium excretion are common. In both disorders, sodium wasting contributes to a chronic mild plasma volume contraction reflected by a normal to low blood pressure despite high renin and angiotensin levels.

The features at clinical presentation vary ( see Table: Some Differences Between Bartter Syndrome and Gitelman Syndrome Some Differences Between Bartter Syndrome and Gitelman Syndrome ).

Both syndromes are usually autosomal recessive Autosomal Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more , although sporadic cases and other types of familial patterns can occur. There are several genotypes of both syndromes (see table Subtypes of Bartter Syndrome Subtypes of Bartter Syndrome* ); different genotypes can have different manifestations ( 1 Etiology reference Bartter syndrome and Gitelman syndrome are autosomal recessive renal disorders characterized by fluid, electrolyte, urinary, and hormonal abnormalities, including renal potassium, sodium, chloride... read more ).

Bartter syndrome tends to manifest prenatally or during infancy or early childhood. Gitelman syndrome tends to manifest during late childhood to adulthood. Bartter syndrome can manifest prenatally with intrauterine growth restriction and polyhydramnios. Different forms of Bartter syndrome can have specific manifestations, including hearing loss, hypocalcemia, and nephrocalcinosis, depending on the underlying genetic defect. Children with Bartter syndrome, more so than those with Gitelman syndrome, may be born prematurely and may have poor growth and development postnatally, and some children have intellectual disability.

Most patients have low or low-normal blood pressure and may have signs of volume depletion. Inability to retain potassium, calcium, or magnesium can lead to muscle weakness, cramping, spasms, tetany, or fatigue, particularly in Gitelman syndrome. Polydipsia, polyuria, and vomiting may be present.

In general, neither Bartter syndrome nor Gitelman syndrome typically leads to chronic renal insufficiency.

Bartter syndrome and Gitelman syndrome should be suspected in children with characteristic symptoms or incidentally noted laboratory abnormalities, such as metabolic alkalosis Metabolic Alkalosis Metabolic alkalosis is primary increase in bicarbonate (HCO3⁻) with or without compensatory increase in carbon dioxide partial pressure (Pco2); pH may be high or nearly normal. Common... read more and hypokalemia Hypokalemia Hypokalemia is serum potassium concentration 3.5 mEq/L ( 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common cause is... read more . Measurement of urine electrolytes shows high levels of sodium, potassium, and chloride that are inappropriate for the euvolemic or hypovolemic state of the patient. Diagnosis is by exclusion of other disorders:

A 24-hour measurement of urinary calcium or the urine calcium/creatinine ratio may help distinguish the two syndromes; the levels are typically normal to increased in Bartter syndrome and low in Gitelman syndrome.

Definitive diagnosis, including identification of disease subtypes, is through genetic testing, which is now becoming more widely available.

Because renal prostaglandin E2 secretion contributes to the pathogenesis in Bartter syndrome, NSAIDs (eg, oral indomethacin 1 to 5 mg/kg once a day) should be given ( 1 Treatment reference Bartter syndrome and Gitelman syndrome are autosomal recessive renal disorders characterized by fluid, electrolyte, urinary, and hormonal abnormalities, including renal potassium, sodium, chloride... read more ); patients are also given oral potassium-sparing diuretics (eg, spironolactone 150 mg 2 times a day or amiloride 10 to 20 mg 2 times a day). Potassium-sparing diuretics alone are used in Gitelman syndrome. Low-dose ACE inhibitors can help limit the aldosterone-mediated electrolyte derangements. However, no therapy can completely eliminate potassium wasting, and oral potassium supplementation (potassium chloride 20 to 40 mEq one or 2 times a day) is often necessary. Magnesium supplements may also be needed.

Exogenous growth hormone can be considered to treat short stature.