What Is Bartter Syndrome

Bartter Syndrome is a rare genetic disorder that affects the kidneys and can lead to a range of health problems. In this article, we will provide simple, plain English explanations for various aspects of Bartter Syndrome, including its types, causes, symptoms, diagnostic tests, treatments, and medications.

Bartter syndrome is a general term for a group of rare genetic disorders in which there are specific defects in kidney function. These defects impair the kidney’s ability to reabsorb salt and cause imbalances in various electrolyte and fluid concentrations in the body. The electrolytes affected are primarily mineral salts such as potassium, calcium, magnesium, sodium, and chloride. The symptoms and severity of Bartter syndrome vary from one person to another and can range from mild to severe. Age of onset of overt symptoms can range from before birth to adulthood. Bartter syndrome is caused by alterations (mutations) in one of several different genes. Treatment is aimed at correcting the electrolyte imbalances through the use of supplements and certain medications such as nonsteroidal anti-inflammatories (NSAIDs) and diuretics.

Types of Bartter Syndrome:

Bartter Syndrome comes in several types, each with its own characteristics:

1. Type I (Classic Bartter Syndrome): This type usually appears in childhood and is caused by mutations in the SLC12A1 gene. It leads to salt wasting, which means the body loses too much salt.
2. Type II (Neonatal Bartter Syndrome): This type typically appears in newborns or infants. Mutations in the KCNJ1 gene cause this form. It also results in salt wasting, along with other electrolyte imbalances.
3. Type III (Bartter Syndrome associated with CLCNKB gene): This type arises in both childhood and adulthood due to mutations in the CLCNKB gene. It causes salt wasting and can be mistaken for Type I or Type II.
4. Type IV (Bartter Syndrome associated with BSND gene): This type is quite rare and is linked to mutations in the BSND gene. It causes similar symptoms as other types but may involve sensorineural deafness.

Causes of Bartter Syndrome:

Bartter Syndrome is primarily caused by genetic mutations that affect the normal functioning of the kidneys. These mutations interfere with the kidney’s ability to reabsorb certain electrolytes, leading to imbalances. The syndrome is not caused by factors like infections or lifestyle choices; it’s something a person is born with.

Bartter syndromes are caused by recessive mutations in the SLC12A1 gene (type 1), the KCNJ1 gene (type 2), the CLCNKB gene (type 3), the BSND gene (type 4A), or both the CLCNKA and CLCNKB genes (type 4B). Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body. Bartter syndrome is inherited in an autosomal recessive manner, except for type 5, which is inherited in an X-linked recessive matter.

Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits two abnormal copies of a gene, one from each parent. If an individual inherits one normal copy and one copy 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 altered gene and 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 is 25%. The risk is the same for males and females.

This is however different for the X-linked Bartter syndrome type 5, as a boy only has one X-chromosome, which he inherits from the mother. If the mother is a carrier for a mutation in MAGED2, then there is a 50% risk that she passes this on to her children. If she passes it on to a daughter, then she will be a carrier, as well, as a daughter also inherits a normal copy of MAGED2 on the X-chromosome she receives from the father. But if she passes it on to a boy, then he will be affected, as he does not have a second normal copy, for he receives the Y-chromosome from the father. Very rarely, girls who are carriers can also have disease manifestations, but it is typically much milder than in boys.

Most of the genes involved in Bartter syndrome produce (encode) proteins that are required for the proper function of the kidneys. One of the different functions of the kidney is maintaining a specific volume and composition of body fluids through the reabsorption of salts and minerals that conduct electrical impulses in the body (electrolytes). Electrolytes are necessary for various functions in the body including nerve firing, muscle contraction, energy generation, and most major biochemical reactions in the body. The kidneys maintain electrolyte balance by filtering the blood. Hair-sized structures called nephrons are the basic functional units of the kidneys and there are roughly a million of these in our kidneys. Each nephron consists of a glomerulus and a renal tubule. The glomeruli filter the blood and in an adult create a primary urine volume of about 100 ml/min (or roughly 150litres per day). This is called the glomerular filtration rate (GFR). The renal tubule then reabsorbs most of this filtrate, including electrolytes such as sodium, chloride and potassium back into the blood to ensure that not too much is lost through the urine. The renal tubule contains four main segments known as the proximal convoluted tube, the loop of Henle, the distal convoluted tube (DCT), and the collecting duct. Bartter syndrome is primarily a disorder in the loop of Henle, but the distal convoluted tubule can also be affected in some subtypes.

The loop of Henle accounts for a significant percentage of the salt and mineral reabsorption in the body. It also plays a role in urine concentration. The DCT plays a lesser role in salt reabsorption and also has a role in functions necessary to maintain chemical balance in the body (e.g. potassium secretion). When one segment of the distal nephron does not function properly, others try to compensate. An important segment for compensation is the collecting duct, where especially the sodium that has not been reabsorbed upstream is taken up, but this occurs in exchange for potassium and acid. It is this compensation that generates the typical electrolyte abnormalities of Bartter syndrome, the low potassium and the alkalosis (lack of acid).

Mutations in the genes involved in Bartter syndrome result in abnormal functioning of the ion channels or proteins involved in the transport of electrolytes back into the bloodstream. This abnormal functioning prevents sodium and chloride (salt) from being reabsorbed from the urine. This causes too much salt and water to be expelled from the body through the urine. In turn, either directly or indirectly, other electrolytes such as potassium, magnesium, and calcium are also affected. Thus, the proper balance of electrolytes in the body is disrupted, and it is this balance which is critical for the normal functioning of our body. These imbalances ultimately lead to the various symptoms of the Bartter syndromes.

Symptoms of Bartter Syndrome:

The symptoms of Bartter Syndrome can vary depending on the type and severity of the condition. Common symptoms include:

1. Excessive thirst: People with Bartter Syndrome often feel very thirsty due to frequent urination, which leads to fluid loss.
2. Frequent urination: The kidneys cannot properly reabsorb water, causing excessive urination and dehydration.
3. Muscle cramps: Low potassium levels can result in muscle cramps and weakness.
4. Fatigue: Dehydration and electrolyte imbalances can lead to tiredness and weakness.
5. Nausea and vomiting: These symptoms may occur due to electrolyte imbalances.
6. Constipation: Electrolyte disruptions can affect the digestive system, causing constipation.
7. Growth problems: Children with Bartter Syndrome may experience growth delays.
8. High blood pressure: In some cases, Bartter Syndrome can lead to high blood pressure.
9. Kidney stones: People with this condition are at a higher risk of developing kidney stones.
10. Metabolic alkalosis: This is a condition where the body’s pH becomes too high due to imbalances in electrolytes.

Diagnostic Tests for Bartter Syndrome:

To diagnose Bartter Syndrome, doctors may perform various tests:

1. Blood tests: These can detect imbalances in electrolytes like potassium and sodium.
2. Urine tests: Urine samples can show excessive salt and potassium in the urine.
3. Genetic testing: DNA tests can identify specific gene mutations associated with Bartter Syndrome.
4. Imaging: Kidney imaging may be done to look for structural abnormalities.
5. Electrocardiogram (ECG): This test can check for irregular heart rhythms, which can be a complication of Bartter Syndrome.

Treatments for Bartter Syndrome:

Bartter Syndrome is a chronic condition, but treatments can help manage symptoms and improve the quality of life:

1. Medications: Doctors may prescribe medications like potassium supplements or diuretics to help balance electrolytes.
2. Salt and fluid intake: Managing salt and fluid intake is crucial to prevent dehydration and electrolyte imbalances.
3. High-calorie diet: Children with Bartter Syndrome may require a high-calorie diet to support growth.
4. Regular check-ups: Monitoring kidney function and electrolyte levels through regular check-ups is essential.
5. Surgery (in severe cases): In some instances, surgery may be necessary to correct kidney or urinary tract abnormalities.

There is no cure for these disorders, which require lifelong administration of certain supplements and medications. The mainstay of treatment is restoring the proper balance of fluids and electrolytes in the body. This typically includes sodium and potassium chloride supplementation to help correct electrolyte imbalances. Potassium chloride supplementation is preferred to other forms of potassium salts because of the corresponding chloride deficiencies. Some infants with severe, life-threatening loop disorders (antenatal Bartter syndromes) may require intravenous salt and water replacement. Because the elevated levels of prostaglandins aggravate the polyuria and electrolyte abnormalities, treatment typically includes a drug that decreases the production of these such as indomethacin, ibuprofen or celecoxib. These drugs are also called nonsteroidal anti-inflammatory drug (NSAID). Indomethacin has generally been used and shown to be effective in individuals with Bartter syndromes, but can have severe side effects, especially in premature babies with regards to perforation in the intestinal tract, especially the stomach. If used, it is recommended to do so in combination with a stomach acid blocker. Newer forms of NSAID, such as celecoxib (also called “COX2 inhibitors”) have a much lower risk of these intestinal side effects and have also been shown to be effective in Bartter syndrome, but there is less experience in their use. With increasing age, Bartter syndrome tends to get easier to manage and control. The most difficult period is usually the first year(s) of life. As there is also concern that long-term use of NSIAD may affect kidney function, these medications often get reduced or weaned off over the years.

Some affected individuals may receive medications known as potassium-sparing diuretics such as spironolactone or amiloride. These drugs increase the excretion of sodium in urine, but retain potassium and acid thereby improving low potassium levels in the blood (hypokalemia) and alkalosis. Yet, because they worsen the loss of sodium, they risk low blood pressure and potentially even collapse (hypovolemic shock) and it is usually recommended to take these together with adequate sodium chloride supplementation.

Drugs that inhibit or block the renin-aldosterone-angiotensin system (RAAS inhibitors) have been used to treat individuals with Bartter syndromes in addition to other therapies (adjunct therapy). RAAS inhibitors include aldosterone antagonists, angiotensin II receptor blockers, and angiotensin-converting enzyme (ACE) inhibitors. These drugs can prevent the secretion of aldosterone from the adrenal glands and counteract the effects of renin on the kidneys, thereby reducing potassium and acid loss. But, like the potassium-sparing diuretics, they may dangerously lower blood pressure, which may already be low in individuals with Bartter syndromes, and can potentially impact kidney and cardiovascular function. Thus, their use should be carefully considered and monitored and the drugs must be stopped, if the patient has additional salt losses, e.g. from diarrhea and/or vomiting.

Medications for Bartter Syndrome:

Several medications can be used to treat Bartter Syndrome and its associated symptoms:

1. Potassium supplements: These help maintain proper potassium levels in the body.
2. Nonsteroidal anti-inflammatory drugs (NSAIDs): They can reduce kidney-related pain and inflammation.
3. Angiotensin-converting enzyme (ACE) inhibitors: These medications may be prescribed to manage high blood pressure.
4. Proton pump inhibitors (PPIs): PPIs can help reduce stomach acid and prevent complications like kidney stones.
5. Loop diuretics: These drugs can help control fluid balance and blood pressure.

Conclusion:

Bartter Syndrome is a complex genetic condition that affects the kidneys and electrolyte balance in the body. It can lead to a range of symptoms and complications, but with proper diagnosis and management, individuals with Bartter Syndrome can lead fulfilling lives. If you suspect you or a loved one may have Bartter Syndrome, it’s essential to seek medical attention for accurate diagnosis and personalized treatment. Remember, Bartter Syndrome is a lifelong condition, but with the right care, its impact can be minimized.

 

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. Thank you for giving your valuable time to read the article.

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