Bartter Syndrome: Symptoms, Causes, Treatment, and More

Bartter syndrome is a rare inherited disorder that impedes the kidneys' ability to reabsorb salt, potassium, calcium, and other electrolytes, leading to the excessive loss of all of these compounds in urine. Also known as salt-wasting nephropathy, Bartter syndrome is characterized by dehydration, fatigue, cramping, weakness, brittle bones, and hardening of the kidneys (glomerulosclerosis). The disease can be diagnosed with blood tests and urinalysis and confirmed with a genetic test. Treatment is directed at managing the symptoms of the disease on a case-by-case basis. There is no cure for Bartter syndrome.

Bartter syndrome is named after Dr. Frederic Bartter who first described the genetic disorder in 1962.

Urine testing — Peter Dazeley / Getty Images

Types of Bartter Syndrome

There are five main types of Bartter syndrome, each associated with a specific gene mutation. Depending on the type involved, symptoms of Bartter syndrome may be apparent at or near the time of birth (antenatal) or later in life.

Type 1: Antenatal
Type 2: Antenatal
Type 3: Considered "classic" Bartter's syndrome with symptoms typically diagnose at school age or later
Type 4: Antenatal
Type 5: Antenatal

Depending on the mutation involved, symptoms can range from mild (as with "classic" type 3) to severe (most especially with types 4 and 5).

The mutations can dictate which type of symptoms develop and whether boys are girls are more likely to be affected.

Symptoms

Bartter syndrome may become apparent before a baby with the condition is born, showing up as an excessive build-up of amniotic fluid (polyhydramnios) between 24 and 30 weeks of gestation.

Newborns with Bartter syndrome typically urinate excessively (polyuria), show signs of excessive thirst (polydipsia), and experience vomiting and diarrhea. Although polyruia in newborns can be life-threatening, the kidney function of some babies with this condition normalizes within weeks and requires no further treatment.

Among the characteristic symptoms of Bartter syndrome:

The excessive loss of salt can lead to dehydration, constipation, salt craving, polyuria, polydipsia, and waking up at night to urinate (nocturia).
The excessive loss of potassium can lead to hypokalemia (low blood potassium) characterized by muscle weakness, cramping, fatigue, heart palpitations, breathing difficulties, digestive problems, and sensorineural hearing loss.
The excessive loss of calcium in urine (hypercalciuria) can impede the development of bone in children and cause osteopenia—weakened bones and bone loss.

Symptoms of Bartter syndrome can vary substantially among children, with some experiencing only mild ones. Those with antenatal symptoms tend tof are worse, mainly because the loss of salt, potassium, or calcium can interfere with normal fetal development.

Causes

Bartter syndrome is an autosomal recessive pattern, meaning that two copies of an abnormal gene—one from the father and one from the mother—must be present in order for the disease to develop.

Bartter syndrome is caused by mutations in one of seven different genes, each of which is associated with a specific type of Bartter syndrome. Additional mutations may result in subtypes with a different range of symptoms or disease severity.

The genes are meant to encode proteins that transport salt and electrolytes like potassium and calcium into the kidneys for reabsorption in the loop of Henle (the U-shaped tubule where water and salt are recovered from urine). If the genes are mutated, the resulting proteins cannot transport some or all of these compounds through the cells of the loop of Henle.

The specific genetic mutations confer to the five main types of Bartter syndrome:

Names	Type	Gene Mutations	Details
Antenatal Bartter syndrome	1	SLC12A1, NKCC2	Tends to be severe with risk of polyhydramnios and premature birth
Antenatal Bartter syndrome	2	ROMK, KCNJ1	Tends to be severe with risk of polyhydramnios and premature birth
Classical Bartter syndrome	3	CLCNKB	Tends to be milder than other forms of the disease
Bartters syndrome with sensorineural deafness	4	BNDS	Tends to be severe with hearing loss caused by antenatal damage to the auditory nerve
Bartter syndrome with autosomal dominant hypocalcemia	5	CASR	Typically severe and affecting mainly boys with growth delays, brittle bones, and hearing loss

Bartter syndrome is rare, affecting only around one of every 1.2 million births. It occurs more often in children born to parents who are consanguineous (closely related). The condition appears to be more common in Costa Rica and Kuwait than in any other population.

There is little research regarding life expectancy in children with Bartter syndrome, but most evidence suggests that the prospects are good if the disease is diagnosed and treated early.

Despite the impact that Bartter syndrome can have on the kidneys, renal failure is rare.

Diagnosis

Bartter syndrome is diagnosed based on a review of symptoms and medical history along with various blood and urine tests. Because the disorder is so rare, input from a geneticist, genetic counselor, and other specialists is often needed.

Blood tests to diagnose Bartter syndrome look for low levels of potassium, chloride, magnesium, and bicarbonate in the blood as well as elevated levels of the hormones renin and aldosterone.

Urinalysis looks for abnormally high levels of sodium, chloride, potassium, calcium, and magnesium in urine as well as the presence of prostaglandin E2 (a marker for kidney inflammation).

The antenatal forms of Bartter syndrome can often be diagnosed before birth when polyhydramnios is detected without the presence of congenital birth defects. There also are elevated levels of chloride and aldosterone in amniotic fluid.

Molecular genetic testing can confirm a diagnosis. There are several genetic tests that can detect the various mutations associated with Bartter syndrome, available only through specialized genetic laboratories.

Additional genetic testing may be needed to differentiate Bartter syndrome from a closely related but milder inherited disorder known as Gitelman syndrome.

Treatment

The primary goal of treating Bartter syndrome is to restore the balance of fluids and electrolytes. How this is done largely depends on the severity of symptoms.

Some children require minimal management or their fluid/electrolyte balance may become normal spontaneously without treatment. Others may require lifelong care from a team of providers, including a pediatrician, general internist, and/or nephrologist.

Medications

Sodium, potassium chloride, and magnesium supplements are often used to correct electrolyte imbalances. Other drugs may be prescribed to treat inflammation and low prostaglandin levels that promote excessive urination, such as nonsteroidal anti-inflammatory drugs (NSAIDs) like Advil (ibuprofen), Celebrex (celecoxib), and Tivorbex (indomethacin).

Stomach acid blockers—like Pepcid (famotidine) and Tagamet (cimetidine)—may be needed to reduce the risk of ulcers and bleeding caused by long-term NSAID use.

Other drugs, such as aldosterone antagonists, angiotensin II receptor blockers, and angiotensin-converting enzyme (ACE) inhibitors, may be needed to reduce renin levels and the risk of kidney damage.

Depending on which electrolytes are imbalanced, some people may require potassium-sparing diuretics such as spironolactone or amiloride to increase the excretion of sodium in urine but retain potassium.

Other Interventions

Kidney transplant can correct severe abnormalities and has, in rare cases, been performed when someone has developed the complication of renal failure.

Infants with severe, life-threatening symptoms may require intravenous (IV) salt and water replacement. Children who fail to thrive often benefit from growth hormone therapy to overcome growth retardation and short stature. Cochlear implants can be used to treat deafness associated with Bartter syndrome type 4.

In addition to supplements and adequate hydration, children may be encouraged to eat foods high in salt and potassium (with monitoring).

As a child with Bartter syndrome gets older, the condition generally becomes easier to manage.

A Word From Verywell

Bartter syndrome is a rare and potentially serious genetic disorder that, if detected early, usually can be managed with diet, medications, and supplements. Even when symptoms are severe, there are treatments available to help restore hearing and correct severe kidney dysfunction.

The outlook for people with Bartter syndrome has improved considerably in recent years. With proper, lifelong management of the disease, including adequate hydration and the maintenance of electrolytes, most people with Bartter syndrome can avoid long-term complications (such as renal failure) and live normal, productive lives.

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