Bartter's syndrome (BS) is a group of conditions involving enlargement of certain kidney cells, blood that is more alkaline than normal, high levels of potassium and chloride in the urine, loss of potassium from the kidneys (renal potassium wasting), dehydration, muscle weakness, muscle cramps, frequent urination, and growth deficiency, potentially resulting in dwarfism. It is thought to be caused by a defect in the body's ability to reabsorb potassium. Individuals with Bartter syndrome have a disturbed acid-base ratio (i.e., an accumulation of base or loss of acid) associated with a loss of potassium (hypokalemic alkalosis). Low amounts of potassium may result from overproduction of a certain hormone (aldosterone) that is essential in controlling blood pressure and regulating sodium and potassium levels (hyperaldosteronism). Even so, the blood pressure of people with Bartter syndrome is normal.
Symptoms and their intensity vary among the various types of Bartter’s syndrome. In general, the syndrome is characterized by growth deficiency, potentially resulting in short stature; muscle weakness, cramps, and/or loss of potassium from the kidneys (renal potassium wasting).
Loss of potassium may result from overproduction of a certain hormone (aldosterone) that is essential in controlling blood pressure and regulating sodium and potassium levels (hyperaldosteronism). Low potassium levels may be associated with a disturbance in an affected individual’s acid-base ratio (i.e., an accumulation of base or loss of acid). This is known as hypokalemic alkalosis.
Specific signs and symptoms associated with Bartter’s syndrome include normal blood pressure, low blood chloride; blood that is more alkaline than normal, high blood levels of the hormones rennin and aldosterone, both of which are involved in the regulation of potassium by the kidney; and high levels of potassium and chloride in the urine.
Of the various types of this syndrome, the one known as Gitelman syndrome appears generally to be the mildest and to present later in life, often in adults without symptoms (asymptomatic) who are found to have lack or loss of potassium (hypokalemia) on routine laboratory testing.
The type called classic Bartter’s syndrome usually presents in infants. Symptoms of the classic type may include salt craving, fatigue, muscle weakness, growth retardation and developmental delay.
The type known as antenatal Bartter’s syndrome is the most severe and may become life-threatening. In the newborn, it may present with fever, vomiting, diarrhea, failure to thrive, growth retardation, facial anomalies such as a triangular face, prominent forehead, large eyes, protruding ears, and drooping mouth, severe electrolyte imbalance; and high potassium and chloride excretion in the urine.
Bartter’s syndrome is thought to be caused by a defect in the body’s ability to reabsorb potassium. As a result, an excessive amount of potassium is excreted from the body. This is known as potassium wasting.
Bartter’s syndrome is usually hereditary and the pattern of inheritance is autosomal recessive. In recent years, researchers have worked to identify the genes associated with the various forms of this syndrome, including subgroups within the antenatal group.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Bartter’s syndrome affects children much more frequently than adults, but it has been reported to occur at all ages. Males and females are affected in equal numbers. The neonatal form of the disorder may be suspected before birth and may be diagnosed in the youngest of newborns. There is no racial, ethnic, or gender predilection.
The diagnosis of Bartter syndrome is usually made on the basis of the results of blood tests. If Bartter syndrome is suspected, the potassium level in the blood will be tested. The combination of low blood potassium concentrations with normal blood pressure is a possible indicator of this disorder. Blood tests will also confirm low blood chloride, and that the blood acid/base balance is skewed towards the base, or that the blood is more alkaline than usual.
Tests to determine the concentration of the hormones renin and aldosterone may also be ordered. High blood levels of these hormones would support the diagnosis of Bartter syndrome.
Further confirmation comes from the high levels of potassium and chloride in the urine. Such signs suggest that the ability of the kidney to control the concentration of these electrolytes is failing or has been lost. These same signs and symptoms can also occur in people who have taken excessive amounts of diuretics or laxatives. Urine tests can be done to exclude these causes.
Treatment of Bartter syndrome depends on the type of the syndrome that is present but focuses primarily on preventing the loss of excessive amounts of potassium. This may include medications, supplements, and a diet rich in potassium. Genetic counseling may be of benefit for patients and their families.
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