Bartter syndrome

The signs and symptoms associated with Bartter syndrome can vary depending on the form of Bartter syndrome an affected individual has.^[3] The antenatal forms (beginning before birth) can be life-threatening, while the classical form, beginning in early childhood, tends to be less severe.^[1]

The antenatal forms of Bartter syndrome (types I, II and IV) may first be characterized by abnormally high levels of amniotic fluid surrounding the affected fetus (polyhydramnios); premature delivery; and possibly life-threatening salt (sodium-chloride) loss.^[1][4] Affected newborns may experience excessive urination (polyuria) and life-threatening episodes of fever and dehydration. Vomiting and diarrhea may also occur. Some affected infants have distinctive facial features (triangular face, prominent forehead, large eyes, protruding ears, and drooping mouth), failure to thrive, delayed growth, and/or intellectual disability.^[3] Individuals with type IV may also have sensorineural deafness (hearing loss caused by abnormalities in the inner ear).^[1]

Classical Bartter syndrome typically becomes apparent in childhood and is characterized by muscle weakness, cramping, spasms, and fatigue. Excessive thirst (polydipsia), excessive urination and the need to urinate at night (nocturia) may also be present. This can lead to dehydration. Some children crave salt. Additional symptoms include constipation, vomiting, elevated body temperature, growth delay and developmental delay.^[3]

Some individuals with Bartter syndrome have significant electrolyte imbalances which can lead to irregular heartbeats (cardiac arrhythmias). This can increase the risk for sudden cardiac arrest. Another complication is excessive levels of calcium in the kidneys (nephrocalcinosis). This can lead to blood in the urine, vomiting, and fever. Over time, this calcium buildup can affect kidney function.^[3]

Bartter syndrome may be caused by mutations in any one of several genes; the genetic cause in each case corresponds to the type of Bartter syndrome each affected individual has. Type I results from mutations in the SLC12A1 gene. Type II is caused by mutations in the KCNJ1 gene. Type III results from mutations in the CLCNKB gene. Type IV can be caused by mutations in the BSND gene or from a combination of mutations in the CLCNKA and CLCNKB genes.^[1]  A final variant, type V, has been associated mutations in the CASR gene.^[2] In some people with Bartter syndrome, the genetic cause of the disorder remains unknown; there may be other genes that cause the condition that have not yet been identified.^[2]

All of these genes are essential for normal kidney function - they are involved in the kidneys' abilities to reabsorb salt. Abnormal changes in these genes impair these abilities, allowing for the loss of excess salt through the urine and also affecting the reabsorption of other things including potassium and calcium. The resulting imbalance of these in the body lead to the signs and symptoms of Bartter syndrome.^[1]

 

Bartter syndrome is usually inherited in an autosomal recessive manner, which means that both copies of the disease-causing gene (one inherited from each parent) have a mutation in an affected individual. Parents who each carry one mutated copy of the gene are referred to as carriers and typically do not have signs or symptoms of the condition.^[1] When two carriers for an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Type V Bartter syndrome is inherited in an autosomal dominant manner, which means that one copy of the altered gene in each cell is sufficient to cause the disorder.^[2] Each child born to a person with an autosomal dominant condition has a 50% chance of inheriting the condition. 

The Genetics Home Reference website has illustrations that demonstrate autosomal recessive and autosomal dominant inheritance.

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Bartter syndrome is usually diagnosed after a combination of tests are performed on an individual with the signs and symptoms of the condition. Laboratory tests include blood tests to measure serum electrolyte levels (specifically magnesium, renin, and aldosterone), and urine tests to determine the presence of prostaglandin E2 and urine electrolytes (including elevated levels of sodium and potassium).^[3]

Antenatal subtypes can be diagnosed before birth (prenatally) when polyhydramnios is present without associated congenital malformations and when there are elevated levels of chloride and aldosterone in the amniotic fluid. Molecular genetic testing can be used to confirm the diagnosis.^[3]

Treatment of Bartter syndrome depends on the specific symptoms present in each individual and may require the coordinated efforts of a team of specialists. The primary focus of treatment is on restoring the proper balance of fluids and electrolytes in the body.^[3] This may include oral potassium (K) supplements, medication such as indomethacin, and potassium-sparing diuretics. In high-stress situations such as illness or trauma, blood electrolyte levels can change rapidly, which may require immediate intravenous treatment.^[2][3] Genetic counseling may benefit affected individuals and their families.^[3]

Medscape Reference has an article containing additional, detailed information about the management and treatment of Bartter syndrome. Click here to view this information.

Currently there is no cure for Bartter syndrome, but treatments are available. Severity of symptoms (and associated complications) vary from person to person. People with Bartter syndrome must take medications consistently, as prescribed, throughout their lifetime. They also must be careful to maintain an adequate fluid and electrolyte balance.^[3] With treatment, prognosis in many cases is good.^[5] However, life expectancy and quality of life may be affected by complications such as growth delays, developmental problems, kidney failure and multiple hospitalizations.^[2][5]