An overview of Bartter Syndrome 

Bartter syndrome is a general term for a group of rare, inherited disorders of the kidney.^1,2,3 Each of the different subtypes of Bartter syndrome affect a specific portion of the kidney tubule, resulting in an inability for kidney to adequately reabsorb salts, leading to loss of salt and water from the body in urine.^2,3,4 The symptoms of Bartter syndrome can range from mild to severe, and the exact symptoms vary from one person to another, with no two cases necessarily looking the same.² 

This article aims to provide an overview of the symptoms and clinical presentation of Bartter Syndrome, including the differences and similarities typically seen between different subtypes. 

Types of Bartter Syndrome

Bartter Syndrome is inherited, caused by mutations in one of several different genes, meaning it is a genetic disorder.^2,4 Through the different causative mutations, Bartter Syndrome can be classified into several subtypes:² 

• Bartter syndrome type 1 (SLC12A1 gene)
• Bartter syndrome type 2 (KCNJ1 gene)
• Bartter syndrome type 3 (CLCNKB gene)
• Bartter syndrome type 4A (BSND gene)
• Bartter syndrome type 4B (CLCNKA and CLCNKB genes)
• Bartter syndrome type 5 (MAGED2 gene)

Bartter Syndrome can also be divided into Classic Bartter Syndrome, where symptoms present after birth, and Antenatal Bartter Syndrome, in which symptoms present before birth. 

• Classic Bartter Syndrome - type 3 
• Antenatal Bartter Syndrome - typically associated with types 1, 2, 4A and 4B² 

Symptoms of Bartter Syndrome 

The age of onset, severity and specific symptoms associated with Bartter Syndrome normally vary greatly from one person to another, even among individuals who have the same genetic mutation.² The severity of the disease also varies widely among patients, with some people experiencing mild symptoms and others having severe, potentially life- threatening complications at birth.^2,4 

Common symptoms of Bartter Syndrome include:^2,5,6

• Growth and developmental delays as children grow older (growth retardation), which may continue into adulthood if the condition is left untreated (short stature)
• Muscle weakness, cramping, and spasms 
• Fatigue 
• Dehydration (despite excessive thirst (polydipsia), excessive urination (polyuria) as well as the need to urinate at night (nocturia) can lead to dehydration)
• Some children may crave salt 
• A general feeling of poor health 
• Low blood pressure (hypotension) 

Specific Symptoms by Type⁶

Classic Bartter Syndrome 

Classic Bartter Syndrome usually starts in early childhood and is less severe than the antenatal form, but still requires careful attention and treatment to allow the child to thrive. Typical symptoms include:

• Growth and developmental delays
• Frequent urination 
• Constipation 
• Hypokalemia (low potassium levels) 

Antenatal Bartter Syndrome 

Antenatal Bartter Syndrome starts before birth and can be very serious, and in some cases life- threatening. Typical symptoms include:

• Excess amniotic fluid (Polyhydramnios) - excessive urine production and abnormal buildup of amniotic fluid around the developing fetus
• Premature birth 
• Severe dehydration and salt wasting, as well as vomiting and diarrhea during the neonatal period (first 28 days after birth)
• Type 4 Bartter Syndrome can also involve congenital sensorineural deafness (deafness at birth)⁶

Clinical Presentation and Diagnosis 

Diagnosis of kidney disorders such as Bartter Syndrome, is usually made by nephrologists (kidney specialists) by focusing on biochemical analysis of the blood and urine. 

Correctly diagnosing Bartter Syndrome is important, as salt and water loss into the urine may be severe, particularly in infants (especially in types 1, 2 and 4 Bartter Syndrome). For this reason, Bartter syndrome is typically identified in infancy or early childhood.³

The earlier a patient develops features of Bartter Syndrome, the more severe their condition will be, meaning antenatal Bartter Syndrome is typically more severe than Classic Bartter Syndrome.³

Clinical Examination: patient history and physical examination 

Bartter Syndrome equally affects people assigned male and female at birth. Infants with Bartter Syndrome typically present with excessive thirst, difficulty with feeding, recurrent vomiting, and are typically lethargic.³ Children may present with vomiting, fatigue, muscle weakness, and muscle spasms or cramps.³ 

In addition, general characteristics of Bartter syndrome include facial features such as a prominent forehead, large eyes, pointed ears and a ‘pouting’ expression.⁶ 

Antenatal Bartter Syndrome can be diagnosed before birth by testing the amniotic fluid in the womb. 

Laboratory Tests

• Blood tests - looking at levels of electrolytes, and checking for high levels of renin and aldosterone
• Urine tests - checking for high levels of sodium, chloride, and potassium

Genetic Testing 

Diagnosis of Bartter Syndrome can be confirmed through genetic testing, which can help ensure the correct diagnosis of the subtype of Bartter Syndrome, as different types of Bartter Syndrome are associated with mutations in specific genes.^5,6Additionally, the family genetic history can also be evaluated by a genetic or kidney specialist. 

Genetic testing can also be used in circumstances where there is a family history of Bartter Syndrome, to identify if the fetus has inherited the genetic mutation.⁶ This is important because Bartter Syndrome is a recessive disorder, meaning it takes two abnormal genes, one from each parent, for the child to be affected. With just one abnormal gene, and one normal gene, the child will be a carrier for the disease, but will not show any symptoms. 

Differential Diagnosis 

Distinguishing from Gitelman Syndrome and other electrolyte disorders 

Gitelman Syndrome has similar clinical presentation to Bartter Syndrome type 3.⁵ However, there are some major differences between the two conditions, including the genes involved, the part of the tubule in the kidney that is affected, and the age at which symptoms begin, with Gitelman Syndrome developing from late childhood, usually from age 6, to adulthood.⁵ 

It is important to ensure the correct diagnosis is made, because the treatments required for each condition are different. 

Complications Associated with Bartter Syndrome 

Overall, the lack of balance of salt, calcium, and potassium in your body can lead to serious complications. 

Long-term Kidney Issues 

Bartter Syndrome results in increased excretion of calcium in the urine, which can lead to harmful kidney stones, due to a build up of calcium deposits in the kidneys.⁵ However, patients with Bartter syndrome rarely need dialysis or a kidney transplant.³ 

In severe cases, the continuous electrolyte imbalances can lead to chronic kidney disease (CKD). 

Cardiovascular Problems

Monitoring electrolyte levels is very important, as imbalances can lead to cardiac arrhythmias, paralysis, and in severe cases, sudden cardiac arrest. This is why regular follow-ups and monitoring are crucial.⁶

Bone density and Growth Concerns

Electrolyte imbalance can reduce bone mineral density, due to low potassium levels and high calcium excretion in the urine. Additionally, the continuous loss of calcium can stimulate secondary hyperparathyroidism, which can lead to increased bone resorption (breaking down of bones to release calcium) and further decreased bone density.⁵ 

Metabolic alkalosis, which is a common condition in Bartter Syndrome, can impact bone turnover and calcium balance, which both contribute to a reduction in bone mineral density. 

Electrolyte imbalance, (chronic low levels of potassium and sodium) as well as magnesium deficiency, can lead to growth retardation. Additionally, Bartter Syndrome is associated with insensitivity to growth hormone, leading to impaired growth. 

Infection 

Patients with Bartter Syndrome are prone to serious infection, and can become seriously ill very quickly with infections such as flu/diarrhoea.³ Often in these cases, admission to hospital for fluids to be replaced intravenously is required, as well as blood tests to identify how much salt and fluid is required.³

Management and Treatment 

The goal of Bartter Syndrome treatments is to increase the body’s level of potassium and salt, in order to compensate for the losses that occur in the urine.^5,6 This is because the imbalance of these electrolytes contributes to the symptoms of the disease.⁶ This can be achieved through the following approaches: 

Medical Treatments 

• Potassium supplements, either in liquid or tablet form, are beneficial to replace the potassium lost in the urine
• Non-steroidal anti-inflammatory drugs (NSAIDs) can be taken to help kidneys reduce potassium and water loss³ 
• Growth hormone for children that are very young⁵ 
• Potassium-sparing Diuretics, which work by retaining the potassium in the body⁶
• Drugs that block the renin-aldosterone-angiotensin system (RAAS inhibitors) can prevent the secretion of aldosterone from adrenal glands, counteracting the effects of renin on the kidneys, reducing potassium loss

Dietary Recommendations 

A diet high in salt and potassium is important.³ Foods high in potassium would be beneficial to incorporate into your diet, including all fruits, vegetables, and potatoes; biscuits containing dried fruit, and toffee, chocolate, and fudge. To preserve the potassium content in food, it is best to avoid boiling foods such as vegetables, as this causes the loss of potassium into the water.³

Magnesium supplementation can also treat muscle spasms, or tetany.⁶

Living with Bartter Syndrome 

Regular Monitoring and Follow-up 

Bartter Syndromes are life-long conditions, and currently have no cure. This means patients need regular monitoring and follow-up appointments to modify and adapt treatments, ensuring symptoms are kept under control.³

However, with careful monitoring and management to address the associated complications and symptoms, Bartter Syndrome can be managed with medications, as well as lifestyle adaptations and supportive care, to support the overall health and development in affected individuals, allowing them to lead a fulfilling life. 

However, it can be difficult living with a chronic condition, and so it is important to look for psychological and social support if you or a loved one has been diagnosed with Bartter Syndrome. Counselling can be beneficial to help you cope with the impact of chronic illness on your mental health, and additionally there are support groups available for Bartter Syndrome, as well as other rare kidney disorders, which can provide both emotional support and practical advice.