Bartter Syndrome Treatment in Delhi, India

Bartter syndrome is a rare inherited disorder characterised by defects in the kidney's ability to reabsorb salt and maintain proper electrolyte balance in the body. This condition affects the kidneys' ability to control the reabsorption of sodium and chloride ions, leading to excessive urinary losses of these electrolytes. As a result, individuals with Bartter syndrome experience electrolyte imbalances, including low levels of potassium, chloride, and sodium in the blood, as well as metabolic alkalosis (an imbalance in the body's acid-base equilibrium).

Bartter syndrome is classified based on the underlying genetic defect. Here's a breakdown of the main types:

• Type I Bartter Syndrome (Antenatal): Caused by mutations in the SLC12A1 gene, responsible for the sodium-chloride-potassium cotransporter (NKCC2) protein. This type is usually severe and presents before birth.
• Type II Bartter Syndrome (Antenatal/Neonatal): Results from mutations in the KCNJ1 gene, affecting the ROMK potassium channel. Similar to type I, it often presents in the newborn period.
• Type III Bartter Syndrome (Classic): Caused by mutations in the CLCNKB gene, affecting the chloride channel ClC-Kb. This is the "classic" form, typically presenting in childhood with less severe symptoms compared to types I and II.
• Type IV Bartter Syndrome: This type has two subtypes:
• Type IVa: Caused by mutations in the BSND gene, affecting the barttin protein.
• Type IVb: Caused by mutations in both CLCNKA and CLCNKB genes. Both subtypes can present before birth or later in childhood and are sometimes associated with hearing loss.
• Type V Bartter Syndrome: This is a recently identified type associated with mutations in either the CASR gene (calcium-sensing receptor) or a combination of CLCNKA and CLCNKB genes.

It's important to note that the severity of symptoms can vary within each type. While some classifications refer to age of onset (antenatal vs. classic), there can be some overlap.

Bartter syndrome is primarily a genetic disorder, so the most significant risk factor is having a family history of the condition. However, there are certain scenarios and conditions that may increase the likelihood of developing Bartter syndrome:

• Family History: Individuals with a family history of Bartter syndrome or related renal disorders are at higher risk. The condition is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to develop the syndrome.
• Consanguineous Marriage: In populations where consanguineous marriages (marriages between blood relatives) are common, the risk of inheriting autosomal recessive disorders such as Bartter syndrome may be higher.
• Certain Ethnicities: Bartter syndrome can occur in people of any ethnicity, but certain populations may have a higher prevalence due to genetic factors. For example, certain variants of Bartter syndrome are more common in specific ethnic groups.
• Premature Birth: Some cases of Bartter syndrome may present in premature infants. Premature birth and associated complications may predispose infants to electrolyte imbalances and renal dysfunction, increasing the risk of developing Bartter syndrome.
• Prenatal Exposure: In rare cases, exposure to certain drugs or toxins during pregnancy may interfere with foetal kidney development, potentially increasing the risk of Bartter syndrome or similar renal disorders.
• Genetic Mutations: Specific genetic mutations associated with Bartter syndrome can increase the risk of developing the condition. Mutations in genes such as SLC12A1, KCNJ1, BSND, and CLCNKB are implicated in various subtypes of Bartter syndrome.

It's important to note that while these factors may increase the likelihood of developing Bartter syndrome, the condition is still relatively rare, and most individuals with risk factors do not develop the syndrome. Additionally, genetic testing and counselling can help identify individuals at risk and provide guidance for family planning and management.

The symptoms of Bartter syndrome can vary depending on the specific type and severity, but some common ones include:

• Excessive Thirst (Polydipsia): Due to salt loss, the body tries to compensate by increasing fluid intake.
• Frequent Urination (Polyuria): The kidneys are unable to reabsorb electrolytes and water effectively, leading to increased urine output.
• Muscle Weakness and Cramps: Electrolyte imbalances, particularly low potassium, can cause muscle weakness, cramps, and fatigue.
• Growth Delays: Chronic electrolyte imbalances and dehydration can hinder growth and development in children.
• Dehydration: Frequent urination and inability to retain fluids can lead to dehydration.
• Constipation: Dehydration and electrolyte imbalances can contribute to constipation.
• High Blood Pressure (Rare): In some cases, particularly with long-standing Bartter syndrome, high blood pressure might develop.

Additional Symptoms in Newborns and Infants

• Premature birth
• Vomiting
• Failure to thrive
• Lethargy

It's important to note that these symptoms can also be caused by other conditions. If you experience any of these symptoms persistently, consulting a doctor is crucial for proper diagnosis.

Diagnosing Bartter syndrome typically involves a multi-step approach:

• Medical History and Physical Examination: The doctor will inquire about your symptoms, family history, and perform a physical exam to look for signs like dehydration or muscle weakness.
• Blood Tests: These tests measure electrolyte levels (sodium, potassium, chloride, etc.), blood pH (acid-base balance), and hormone levels (renin and aldosterone) which are often abnormal in Bartter syndrome.
• Urine Tests: Urine tests assess electrolyte levels and other substances in the urine to identify patterns suggestive of Bartter syndrome.
• Genetic Testing: While not always necessary for diagnosis, genetic testing can confirm the specific type of Bartter syndrome by identifying mutations in the responsible genes. This can help determine the most appropriate treatment approach and provide information about potential risks for future pregnancies.
• Imaging Tests: In some cases, imaging tests like ultrasounds might be used to evaluate the kidneys for any structural abnormalities.

Early diagnosis and prompt treatment are crucial for managing Bartter syndrome effectively and preventing potential complications.

Treatment for Bartter syndrome aims to correct electrolyte imbalances, alleviate symptoms, and prevent complications. The management approach may vary depending on the severity of symptoms and the specific subtype of Bartter syndrome. Here are common treatment modalities:

• Electrolyte Supplementation: Oral supplements of potassium and magnesium are often prescribed to correct hypokalemia and hypomagnesemia. These supplements help restore electrolyte balance and alleviate symptoms such as muscle weakness and fatigue.
• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): NSAIDs such as indomethacin may be prescribed to inhibit prostaglandin synthesis and reduce renal potassium wasting. This can help maintain potassium levels and prevent hypokalemia.
• Potassium-Sparing Diuretics: In some cases, potassium-sparing diuretics like spironolactone or amiloride may be used to counteract renal potassium wasting and conserve potassium. These medications are often used in conjunction with other therapies to manage electrolyte imbalances.
• High-Salt Diet: Consuming a diet rich in salt (sodium chloride) can help compensate for the renal salt wasting characteristic of Bartter syndrome. Salt supplementation may be necessary, especially during episodes of increased fluid loss through sweating or diarrhoea.
• Fluid Replacement: Adequate hydration is essential to prevent dehydration, especially in individuals experiencing polyuria and polydipsia. Maintaining proper fluid balance helps prevent complications such as electrolyte disturbances and kidney damage.
• Proton Pump Inhibitors (PPIs): PPIs may be prescribed to reduce gastric acid secretion and minimise the risk of gastric ulcers, which can occur due to metabolic alkalosis and elevated urinary chloride excretion in Bartter syndrome.
• Monitoring and Follow-Up: Regular monitoring of electrolyte levels, renal function, blood pressure, and growth parameters is crucial for managing Bartter syndrome. Adjustments to treatment plans may be necessary based on individual responses and changes in symptoms.
• Genetic Counselling: Genetic counselling should be offered to affected individuals and their families to provide information about the inheritance pattern of Bartter syndrome, recurrence risks in future pregnancies, and available reproductive options.
• Education and Support: Providing education and support to patients and their families regarding the condition, dietary modifications, medication adherence, and symptom management is essential for optimising outcomes and quality of life.

Bartter syndrome can lead to various complications, primarily due to chronic electrolyte imbalances and renal dysfunction. Some of the potential complications associated with Bartter syndrome include:

• Dehydration: Excessive urination (polyuria) and fluid loss can lead to dehydration, which may manifest as dry mouth, decreased urine output (oliguria), thirst, fatigue, and lightheadedness.
• Electrolyte Imbalances: Bartter syndrome is characterised by electrolyte disturbances, including hypokalemia (low potassium levels), hypomagnesemia (low magnesium levels), and metabolic alkalosis (elevated blood pH). These imbalances can cause muscle weakness, cramps, cardiac arrhythmias, and neurological symptoms.
• Renal Complications: Prolonged electrolyte imbalances and renal salt wasting can lead to kidney damage, including nephrocalcinosis (calcium deposits in the kidneys), nephrolithiasis (kidney stones), and progressive renal insufficiency.
• Growth and Developmental Delays: Children with Bartter syndrome may experience delays in growth and development due to chronic electrolyte imbalances and hormonal disturbances.
• Cardiovascular Effects: Electrolyte imbalances, particularly hypokalemia, can affect cardiac function and increase the risk of arrhythmias, palpitations, and cardiac arrest.
• Musculoskeletal Complications: Chronic potassium depletion can lead to muscle weakness, cramps, and tetany. In severe cases, muscle paralysis or rhabdomyolysis (muscle breakdown) may occur.
• Gastrointestinal Symptoms: Electrolyte disturbances can cause gastrointestinal symptoms such as nausea, vomiting, abdominal pain, and constipation.
• Metabolic Disturbances: Metabolic alkalosis resulting from excessive renal chloride and potassium loss can lead to alterations in acid-base balance and metabolic processes, potentially causing confusion, irritability, and cognitive impairment.
• Endocrine Abnormalities: Bartter syndrome may affect the renin-angiotensin-aldosterone system, leading to abnormal hormone levels and associated symptoms such as hypertension, polyuria, and polydipsia.
• Osteopenia and Bone Disorders: Chronic electrolyte imbalances and hormonal disturbances can affect bone metabolism, leading to decreased bone density (osteopenia) and an increased risk of fractures and skeletal deformities.

Overall, early diagnosis and appropriate management of Bartter syndrome are essential for preventing complications and optimising long-term outcomes. Regular monitoring of electrolyte levels, renal function, growth parameters, and cardiovascular health is crucial for individuals with Bartter syndrome to minimise the risk of complications and improve quality of life.

Which diuretic causes Bartter syndrome?

Diuretics are medications that increase urine output. While some diuretics can cause temporary electrolyte imbalances, they typically wouldn't cause Bartter syndrome. Bartter syndrome is a genetic disorder, not caused by medication.

What is the difference between Bartter and Liddle syndrome?

Bartter syndrome and Liddle syndrome are both rare genetic disorders that affect renal sodium handling, but they differ in their underlying mechanisms. Bartter syndrome involves defects in ion channels or transporters in the thick ascending limb of the loop of Henle, leading to renal salt wasting. In contrast, Liddle syndrome is characterised by mutations affecting the epithelial sodium channel (ENaC) in the distal tubules and collecting ducts, resulting in sodium retention and hypertension.

Who treats Bartter syndrome?

Bartter syndrome is typically managed by a multidisciplinary team of healthcare professionals, including paediatric nephrologists,endocrinologists, dietitians, and genetic counsellors. Treatment may involve medications to correct electrolyte imbalances, dietary modifications, and supportive care to address associated complications.

What is the difference between Bartter syndrome and hyperaldosteronism?

Bartter syndrome and hyperaldosteronism are both conditions that can lead to electrolyte imbalances and hypertension, but they have different underlying causes. Bartter syndrome is a genetic disorder characterised by defects in renal tubular ion transporters, resulting in renal salt wasting and potassium wasting. Hyperaldosteronism, on the other hand, involves excessive production of aldosterone, a hormone that promotes sodium retention and potassium excretion, typically due to adrenal gland abnormalities.

Is Bartter syndrome curable?

Bartter syndrome is not curable as it is a genetic disorder. However, with appropriate medical management, including medications and dietary adjustments, symptoms can be controlled, and individuals with Bartter syndrome can lead relatively normal lives.

Does Bartter syndrome go away?

Bartter syndrome is a lifelong condition since it is caused by genetic mutations. However, with proper treatment and management, symptoms can be controlled, and individuals with Bartter syndrome can lead healthy lives.

What age does Bartter's syndrome occur?

Bartter syndrome can occur at any age, but it often presents in infancy or early childhood. Symptoms typically manifest in the neonatal period or infancy, although milder forms may present later in childhood or even adulthood.

Can adults get Bartter syndrome?

While Bartter syndrome often presents in infancy or childhood, it can also be diagnosed in adults. In some cases, individuals may have mild or atypical presentations that are not recognized until adulthood.

What is mutation in Bartter's syndrome?

Bartter syndrome is genetically heterogeneous, meaning it can result from mutations in several genes encoding ion channels and transporters in the kidney. Mutations in genes such as SLC12A1 (encoding the Na-K-2Cl cotransporter NKCC2) and KCNJ1 (encoding the renal outer medullary potassium channel ROMK) are commonly associated with Bartter syndrome. These mutations disrupt ion transport in the thick ascending limb of the loop of Henle, leading to the characteristic features of the syndrome.

Reviewed by Dr Yogesh Kumar Chhabra , Principal Consultant – Nephrology, Kidney Transplant on on 10 Apr 2024.