What causes Bartter Syndrome?

Bartter syndrome is a group of rare inherited disorders that affect the kidneys’ ability to reabsorb electrolytes, particularly sodium, chloride, and potassium. It is caused by mutations in genes that encode proteins essential for proper functioning of the kidney tubules.

The specific genetic causes of different types of Bartter syndrome are:

1. Classic Bartter Syndrome:
   Mutations in the SLC12A1 gene, which encodes the sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle in the kidney.
2. Antenatal Bartter Syndrome (also called Hyperprostaglandin E Syndrome):
   Mutations in the KCNJ1 gene, which encodes the inwardly rectifying potassium channel (ROMK) in the thick ascending limb and distal convoluted tubule.
3. Classic Bartter Syndrome with Sensorineural Deafness:
   Mutations in the BSND gene, which encodes the barttin subunit of the chloride channels ClC-Ka and ClC-Kb in the kidney and inner ear.
4. Digenic Bartter Syndrome:
   Mutations in both the CLCNKA and CLCNKB genes, which encode the chloride channels ClC-Ka and ClC-Kb, respectively.

All these genetic defects lead to impaired reabsorption of sodium, chloride, and potassium in the kidney tubules, resulting in excessive excretion of these electrolytes in the urine. This electrolyte imbalance is the underlying cause of the symptoms seen in Bartter syndrome.

The syndrome is inherited in an autosomal recessive pattern, except for the digenic form which involves mutations in two different genes.

In some cases, the genetic mutations occur spontaneously and are not inherited from parents. Genetic testing can help identify the specific gene mutation responsible for an individual’s Bartter syndrome.

What are the symptoms of Bartter Syndrome?

Bartter syndrome is characterized by a set of symptoms that arise due to the abnormal handling of electrolytes (sodium, potassium, and chloride) by the kidneys. The main symptoms include:

1. Excessive urination (polyuria) and excessive thirst (polydipsia)
   Due to impaired reabsorption of sodium and chloride, large amounts of urine are produced, leading to dehydration and increased thirst.
2. Electrolyte imbalances

• Low levels of potassium in the blood (hypokalemia)
• Metabolic alkalosis (increased blood pH)
• Low levels of sodium and chloride

1. Growth retardation
   Children with Bartter syndrome often have short stature and delayed growth due to the effects of chronic potassium and calcium deficiencies.
2. Muscle cramps and weakness
   Hypokalemia (low potassium) can cause muscle cramps, fatigue, and weakness.
3. Kidney stones (nephrocalcinosis)
   Increased calcium excretion in the urine can lead to the formation of kidney stones.
4. Constipation
   Poor intestinal absorption of certain electrolytes can cause constipation.
5. Sensorineural deafness (in some types)
   Specific genetic mutations in Bartter syndrome can also affect the inner ear, causing permanent hearing loss.

Symptoms typically begin in early childhood, but the severity can vary depending on the specific genetic subtype. Antenatal Bartter syndrome is the most severe form, with symptoms appearing before birth and leading to polyhydramnios (excess amniotic fluid) during pregnancy.

Other features may include fever, vomiting, failure to thrive, and developmental delays if the condition is not properly managed. Early diagnosis and treatment by your healthcare provider are important to prevent complications and improve outcomes.

What is the Treatment for Bartter Syndrome?

The treatment for Bartter syndrome primarily aims to correct the electrolyte imbalances and manage the associated symptoms. The specific treatment approach may vary depending on the subtype and severity of the condition. Common treatments include:

1. Electrolyte replacement:

• Oral potassium supplements to correct hypokalemia (low potassium levels)
• Sodium and chloride supplements to replace excessive losses
• Intravenous electrolyte replacement may be required in severe cases

1. Medications:

• Potassium-sparing diuretics (e.g., amiloride, spironolactone) help reduce potassium loss
• Non-steroidal anti-inflammatory drugs (NSAIDs) may be prescribed to reduce prostaglandin levels and improve sodium reabsorption
• Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) can help conserve potassium

1. Dietary modifications:

• High-sodium diet to compensate for excessive sodium losses
• Increased potassium intake from foods like bananas, potatoes, and tomatoes
• Adequate fluid intake to prevent dehydration

1. Treatment of complications:

• Medications to treat nephrocalcinosis (kidney stones)
• Growth hormone therapy for severe growth retardation
• Hearing aids or cochlear implants for sensorineural deafness

1. Supportive care:

• Regular monitoring of electrolyte levels, kidney function, and growth
• Physical therapy for muscle cramps and weakness
• Genetic counseling for families

In severe cases, particularly with antenatal Bartter syndrome, additional treatments like indomethacin or dialysis may be required in the neonatal period.

With appropriate treatment and management, most individuals with Bartter syndrome can lead relatively normal lives, although some may experience persistent electrolyte issues, growth problems, or other complications.

Early diagnosis and initiation of treatment are crucial to prevent long-term complications and improve outcomes.