An Overview of Bartter Syndrome

This rare genetic disorder causes excessive loss of salt and potassium

Urine testing

Getty Images / Peter Dazeley

In This Article
Table of Contents

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 (nephro- meaning "kidneys" and -pathy meaning "disease"), Bartter syndrome is characterized by dehydration, fatigue, cramping, weakness, brittle bones, and hardening of the kidneys (glomerulosclerosis).

There are five main types of Bartter syndrome, three of which generally present before or around birth. Of the other two types, one is less severe and can present later in life, and one has an autosomal dominant inheritance and can cause low calcium and low magnesium.

The disease can be diagnosed with blood tests and urinalysis and confirmed with a genetic test. Treatment is directed at managing the symptoms on a case-by-case basis. There is no cure for Bartter syndrome.

The disease is named after Dr. Frederic Bartter who first described the syndrome in 1962.

Symptoms

Symptoms of Bartter syndrome are related to the excessive loss of salt (sodium chloride), potassium, and calcium in urine, each of which has potentially serious consequences. Together, they characterize a disorder in which children often fail to grow and gain weight at the expected rate (referred to as failure to thrive).

Among the characteristic symptoms of Bartter syndrome:

  • The excessive loss of salt can lead to dehydration, constipation, salt craving, increased urination (polyuria), increased thirst (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 hearing loss.
  • The excessive loss of calcium in urine (hypercalciuria) can impede the development of bone in children and cause the weakening of bones (osteopenia).

Symptoms can vary substantially, will some children only experiencing mild symptoms. Those with antenatal symptoms tend to fare worse, mainly because the loss of salt, potassium, or calcium can interfere with normal fetal development.

In severe cases, the signs and symptoms of Bartter syndrome will be seen before birth. The abnormal kidney function can lead to a buildup of amniotic fluid around the developing fetus (polyhydramnios), triggering premature birth. Excessive urination in newborns can often be life-threatening. Vomiting and diarrhea may also occur.

Despite the severity of these episodes, the kidney function of babies can sometimes normalize within weeks and require no further treatment.

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 confers to 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 and osteopenia

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 the symptoms and medical history along with various blood and urine tests to identify imbalances in salt, potassium, calcium, and other electrolytes levels. Because the disorder is so rare, input from a geneticist, genetic counselor, and other specialists would almost invariably be needed.

Blood tests used to diagnose Bartter syndrome will 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 will be used to look 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 would also be 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 mainstay of treatment of Bartter syndrome is the restoration of the balance of fluids and electrolytes in the body. The approach can vary from person to person based on the severity of symptoms. Some children may require minimal management or spontaneously normalize with no need for further treatment. Others may require lifelong care from a team of providers, including a pediatrician, general internist, 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 reduced prostaglandin levels that promote excessive urination, including nonsteroidal anti-inflammatory drugs (NSAIDs) like Advil (ibuprofen), Celebrex (celecoxib), or Tivorbex (indomethacin). 

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

Other drugs, like 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 the abnormality 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, diets will be tailored to increase potassium and salt intake. In addition to adequate hydration, children are encouraged to indulge in salty foods, based on determined need and monitoring.

With increasing age, Bartter syndrome tends to get easier to manage and control.

Was this page helpful?

Article Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial policy to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Bartter FC, Pronove P, Gill JR, MacCardle RC. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis. A new syndromeAm J Med. 1962;33(6):811-28. doi:10.1016/0002-9343(62)90214-0

  2. Al Shibli A, Narchi H. Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations. World J Methodol. 2015 Jun 26;5(2):55-61. doi:10.5662/wjm.v5.i2.55

  3. Kaur A, Webb NJA, Shenoy M, Hulton SA (2018) Bartter Syndrome, 15-year Experience in the United Kingdom. J Rare Disord Diagn Ther. 2018;4:3. doi:10.21767/2380-7245.100173

Additional Reading