What is Bartter Syndrome?
Bartter syndrome is a genetic disorder that affects the body’s ability to reabsorb salt, which results in a depletion of body fluid, often with low to normal blood pressure. It brings about imbalances in electrolytes such as lower levels of potassium and chloride, and in some instances, reduced magnesium. Patients may also show increased levels of renin, a condition known as secondary hyperaldosteronism, and high levels of a substance called prostaglandin E2. Additionally, a condition known as metabolic alkalosis is commonly present, which affects the body’s pH balance.
This syndrome often becomes apparent during infancy, typically marked by a child’s failure to grow at a normal rate. The condition is varied and is classified based on where in the body the salt transportation is affected.
Key forms of this disorder include neonatal (antenatal) Bartter syndrome, classical Bartter syndrome, and Gitelman syndrome.
What Causes Bartter Syndrome?
Bartter syndrome is a condition that affects how sodium, potassium, and chloride are transported within a part of the kidney called the thick ascending limb of the loop of Henle (TALH). When this process is disrupted, these substances are not properly absorbed and this leads to the symptoms of Bartter syndrome.
There are various types of Bartter syndrome:
* Type I is caused by changes in the gene responsible for managing sodium, chloride, and potassium transportation (NKCC2).
* Type II occurs due to mutations in the ROMK gene.
* Type III happens because of changes in the gene that controls chloride channels (CLC-Kb).
* Type IV results from mutations that disrupt the function of a gene known as barttin.
* Type V is caused by mutations in genes related to calcium ion sensing and the chloride channel subunits, ClC-Ka and ClC-Kb.
In some cases, Bartter syndrome can develop after the use of certain antibiotics, called aminoglycosides. This might lead to low levels of potassium, magnesium, and calcium in the body, a condition known as metabolic alkalosis.
There’s also a version of Bartter syndrome that can occur before birth and manifests with severe symptoms. Types III and V usually show up later in life and tend to have milder symptoms.
Risk Factors and Frequency for Bartter Syndrome
Bartter Syndrome is a rare condition, occurring in about 1 in 1,000,000 people. It’s less common than Gitelman Syndrome.
Signs and Symptoms of Bartter Syndrome
Bartter syndrome is often found in children and teenagers who are not growing as expected and are experiencing symptoms like frequent urination, extreme thirst, muscle cramps, vomiting, dehydration, constipation, delayed growth, and failure to thrive. They may be very thin and have noticeable features like a large forehead, big eyes, crossed eyes, protruding ears, hearing loss, and a drooping mouth. They typically have normal or low blood pressure, although long-term cases may have high blood pressure.
It’s important to gather a detailed personal and family history, especially looking for any evidence of kidney stones in the family and ruling out any chances of hidden vomiting or misuse of water pills. This information is crucial before diagnosing Bartter syndrome.
Babies born with antenatal Bartter syndrome often cause their mothers to have too much amniotic fluid during pregnancy because they urinate frequently in the womb. These babies are typically born prematurely. After birth, these babies commonly experience symptoms like fever, hearing loss, excessive urination, vomiting, diarrhea, and dehydration.
Testing for Bartter Syndrome
The diagnosis of Bartter syndrome is based on the patient’s medical history, physical exam, and specific lab test results. Bartter syndrome is often indicated by abnormalities in electrolytes and the body’s acid-base balance. It commonly presents with low potassium levels and metabolic alkalosis.
Some other abnormal findings could include increased levels of the hormones renin and aldosterone in the blood. Conversely, some patients might show low levels of magnesium and phosphate. In terms of urine tests, patients with Bartter syndrome often excrete high amounts of sodium, potassium, and PGE2. High calcium excretion over a 24-hour period helps differentiate Bartter syndrome from Gitelman syndrome, which typically presents with low calcium excretion. Measuring the concentration of chloride in a urine sample can be helpful, too. If chloride levels are less than 25 meq/L, it might suggest a different cause like surreptitious vomiting. But, in Bartter syndrome, chloride levels are usually higher than 35 meq/L.
For newborns suspected to have Bartter syndrome, an ultrasound could show excessive amniotic fluid (polyhydramnios) and slowed fetal growth (intrauterine growth retardation). The level of chloride in the amniotic fluid could also be high.
Various imaging tests, such as abdominal X-rays, intravenous pyelograms (IVP), ultrasound of the kidneys, or spiral CT scans, could be done to check for a condition called nephrocalcinosis (calcium deposits in the kidneys). In some cases, genetic testing might be done to identify specific mutations related to Bartter syndrome.
Treatment Options for Bartter Syndrome
In the early stages of a newborn’s life, they may need an infusion of saline, which is a salt solution. The goal here is to regulate the levels of potassium in the blood. This can be done take potassium orally through supplements such as KCL, which is given in doses ranging between 25 to 100 millimoles per day.
Certain medications such as ACE inhibitors and angiotensin receptor blockers (ARB) are also used to reduce high angiotensin II and aldosterone levels. These drugs can limit protein in the urine and help to increase potassium levels in some instances. Other treatment options include medications like amiloride, spironolactone, and NSAID like indomethacin which can balance increased urine PGE2 levels.
Meanwhile, a magnesium supplement may also be suggested, as low levels of magnesium may worsen the loss of potassium.
If you have abnormal kidney tubules, you’ll be relieved to know these issues usually go away without reoccurring after having a kidney transplant.
What else can Bartter Syndrome be?
These are different conditions that doctors can consider if someone is showing signs of being sick but it’s not clear what the exact issue is. Here are some of the possibilities:
- Diuretic misuse
- Frequent cycles of intense vomiting
- Hyperprostaglandin E syndrome, a rare genetic disorder affecting how the kidneys function
- Familial hypomagnesemia with hypercalciuria/nephrocalcinosis, another genetic disorder which is characterized by low levels of magnesium in the blood
- Pyloric stenosis, which is a condition that can cause vomiting in infants
- Gitelman syndrome, which affect’s person’s ability to reabsorb salt in the kidneys
- Cystic fibrosis, a life-threatening genetic disorder that severely damages the lungs and digestive system
- Gullner syndrome, also known as familial hypokalemic alkalosis with proximal tubulopathy, it’s a condition that causes the kidneys not to function properly
- Excessive mineralocorticoids which are hormones that help maintain salt (sodium) and water balance in the body
- Anomalies in the calcium-sensing receptor (CaSR), which helps maintain calcium balance in the body
- Hypomagnesemia, a condition characterized by low levels of magnesium in the blood
- Congenital chloride diarrhea, a genetic disorder affecting the body’s ability to absorb chloride
- Hypochloremic alkalosis, a disorder where there’s too much alkali in the body and low chloride levels in the blood
- Hypokalemia, which means there is not enough potassium in the blood.
With this diverse set of possibilities, the doctors perform certain tests and evaluations to identify the actual problem behind symptoms.