DEFINITION
Bartter syndrome is a rare inherited defect in the thick ascending limb of the loop of Henle. It is characterized by low potassium levels (hypokalemia), increased blood pH (alkalosis), and normal to low blood pressure.
EPIDEMIOLOGY
The exact prevalence of this disorder is unknown, although it likely affects about 1 per million people worldwide. Annual incidence is estimated at 1/830,000. The condition appears to be more common in Costa Rica and Kuwait than in other populations (Bartter's epidemiology)
PATOGENESIS
It is clinically classified into antenatal or neonatal (type 1 , 2 , 4) and classic (type 3) e some of the 4), as well as five subtypes based on the underlying mutant gene; SLC12A1 (BS I), KCNJ1 (BS II), CLCNKB (BS III),BSND (BS IV) and CASR (BS V).
The genes associated with Bartter syndrome play important roles in normal kidney function. The proteins produced from these genes are involved in the kidneys' reabsorption of salt at the level of Henle's loop . Mutations in any of the five genes impair the kidneys' ability to reabsorb salt, leading to abundant losses of Na+ and Cl- in the urine (salt wasting). This causes a rise in the level of the hormone aldosterone and makes the kidneys remove too much K+ from the body. The condition also results in an abnormal acid balance in the blood called hypokalemic alkalosis, which causes too much Ca++ in the urine.
Four of the genetic variants of Bartter syndrome are transmitted following an autosomal recessive pattern. They are caused by homozygous or compound heterozygous mutations in four genes encoding proteins involved in chloride reabsorption in the ascending part of Henle's loop: SLC12A1 gene (15q15-21), encoding the sodium-potassium-chloride cotransporter NKCC2 in type I Bartter syndrome; KCNJ1 gene (11q21-25) encoding the potassium channel ROMK in type II; CLCNKB gene (1p36), encoding a basolateral chloride channel, in type III; and BSND gene (1p31), encoding barttin, a subunit for the chloride channel, in type IV. A final variant (type V) is transmitted as an autosomal dominant trait, and is associated with heterozygous activating mutations of the CASR gene (3q13.3-q21), encoding the calcium receptor (Bartter's patogenesis )
SYMPTOMS
Bartter’s Syndrome was first discovered in 1962 by Frederic Bartter. Bartter described this syndrome in two African-American patients: a 5 year old boy and a 25 year old man with a long history of slow growth, weakness and fatigue. On high sodium diets, both patients had normal blood pressure and high urinary aldosterone excretion, resulting in metabolic alkalosis. Initially, it was considered a vascular disease. In the 1970′s, when prostaglandins were discovered, it was found that Bartter’s Syndrome patients overproduced prostaglandins. If treated with a prostaglandin inhibitor, aldosterone levels returned to normal. Plasma potassium levels did not. Subsequently, experimental potassium deficiency induced prostaglandin production and many of the symptoms of Bartter’s Syndrome. The suggested problem was not intravascular, but a renal tubular problem.
Patients with this syndrome share a a lot of clinical symptoms.
Most notable are:
dehydratation
costipation
polyuria
osteopenia
muscle cramping and weakness
fatigue
hearing loss
(Bartter's symptoms)
DIAGNOSIS
The diagnosis of Bartter syndrome is usually suspected when low levels of potassium are seen in the blood (hypokalemia). The potassium level is usually less than 2.5 mEq/L. Unlike other forms of kidney disease, this condition does not cause high blood pressure and there is a tendency toward low blood pressure, even if there are also elevated plasma renin and aldosterone levels that causes hypertension in a normal healthy person. Moreover this desease is characterized by the presence of metabolic alkalosis caused by high urine chloride levels.
In conclusion, a biopsy of the kidney typically shows too much growth of kidney cells called the juxtaglomerular apparatus, so there is a hyperplasia of these cells. However, this is not found in all patients, especially in young children. (Bartter's diagnosis)
THERAPY
There is no cure for Bartter’s syndrome. The treatments consist of supplements to replace what is lost, like potassium and chloride supplements, and medications to prevent urinary wasting of potassium and magnesium. In younger children growth hormone may be used to prevent the short stature and prostaglandin inhibitors to decrease the elevated prostaglandin levels.
In stressful situations (additional diseases, surgical procedures, trauma) blood electrolyte levels may change rapidly, requiring prompt and vigorous intravenous treatment.
Life expectancy may be reduced in severe cases but renal failure is rare. Quality of life may be poor, growth rate reduced, and medicalization/hospitalization rate high. (Bartter's therapy)
