Bartter syndrome: What you need to know

From the desk of Robb Wolf

Most folks haven’t heard of Bartter syndrome. This genetic disorder of impaired electrolyte absorption <a href="https://www.ncbi.nlm.nih.gov/books/NBK442019/" target="_blank" rel="noopener noreferrer">affects</a> just 1 out of every 1,000,000 people.But in a world of eight billion humans, one in a million begins to add up. That’s why I wrote this article: because many thousands of people and their loved ones could benefit from the information.The pathophysiology of Bartter syndrome mostly revolves around losing (or not absorbing) the electrolytes sodium, chloride, <a href="https://drinklmnt.com/blogs/health/potassium-benefits-and-best-sources" target="_blank" rel="noopener noreferrer">potassium</a>, magnesium, and calcium.A hallmark of the disorder, excessive urination, can lead to further complications as the symptoms of Bartter syndrome are often present even before birth. Excess urination by the fetus can cause the uterus to swell with amniotic fluid and disrupt prenatal development.Bartter syndrome can be quite tricky to identify, diagnose, and manage. Some people have only mild symptoms, and the presentation can mimic those of other genetic disorders like <a href="https://drinklmnt.com/blogs/health/gitelman-syndrome" target="_blank" rel="noopener noreferrer">Gitelman syndrome</a>.Replacing electrolytes doesn’t cure the syndrome. Bartter is a genetic disorder, after all. But the mainstay of treatment is to replace these minerals. Maintaining fluid and electrolyte levels can at least help prevent the <a href="https://drinklmnt.com/blogs/health/what-causes-muscle-cramps" target="_blank" rel="noopener noreferrer">muscle cramps</a>, fatigue, weakness, dizziness, brain fog, etc. that come with the disorder.Today will be a deep dive into Bartter syndrome. You’ll learn how it presents, what causes it, how to diagnose it, and the most practical treatment options. Let’s get started.<h2>What Is Bartter Syndrome?</h2>Bartter syndrome, also known as salt-losing tubulopathy with secondary hyperaldosteronism, is a group of genetic disorders in which the kidneys <a href="https://www.ncbi.nlm.nih.gov/books/NBK442019/" target="_blank" rel="noopener noreferrer">can’t</a> properly absorb salt. Since salt is essential for maintaining blood volume, those with the disorder tend to have low blood volume and low blood pressure.Sodium and chloride (salt) aren’t the only electrolytes affected by Bartter syndrome. You also see imbalances in potassium (<a href="https://drinklmnt.com/blogs/health/low-potassium-symptoms-and-best-sources" target="_blank" rel="noopener noreferrer">hypokalemia</a>), calcium, and sometimes magnesium.These electrolyte imbalances are closely linked to hormonal disruptions that occur with Bartter syndrome. In particular, you see elevations in two hormones—renin and aldosterone—that regulate electrolyte levels, <a href="https://drinklmnt.com/blogs/health/what-electrolytes-do-for-you" target="_blank" rel="noopener noreferrer">fluid balance</a>, and blood pressure.Bartter isn’t just one condition, but several—and the different types are classed by their respective genetic mutations. I’ll cover this more in the causes section.First, though, I want to discuss the long (and often confusing) list of Bartter syndrome symptoms.<h2>Symptoms of Bartter Syndrome</h2>The symptoms of Bartter syndrome run the gamut. Why? Because the symptoms of <a href="https://drinklmnt.com/blogs/health/electrolyte-imbalance-or-deficiency" target="_blank" rel="noopener noreferrer">electrolyte imbalance</a> also run the gamut.And sometimes, there aren’t any symptoms at all. Those with low serum potassium (hypokalemia), for instance, are often (relatively) asymptomatic.But that doesn’t mean there isn’t a problem. As hypokalemia progresses, the patient may experience cardiac arrhythmias and other heart function irregularities. These symptoms, though rare, can be fatal if left untreated.The symptoms of a salt imbalance (low sodium and chloride) tend to be more noticeable. This is due in part to the fact that low sodium is, arguably, the more dangerous of our electrolyte imbalance problems because it can worsen issues of low potassium. <a href="https://drinklmnt.com/blogs/health/symptoms-of-low-sodium-and-how-to-treat-hyponatremia" target="_blank" rel="noopener noreferrer">Low sodium symptoms</a> include muscle cramps, fatigue, headaches, malaise, irritability, weakness, dizziness, confusion, and salt cravings.Another common symptom of Bartter syndrome is polyuria, or the production (and loss) of large amounts of dilute urine. Polyuria not only disrupts electrolyte levels, but also fluid levels. Dehydration is a real concern.People with Bartter syndrome tend to experience excessive thirst as well, which somewhat mitigates the risk of <a href="https://drinklmnt.com/blogs/health/dehydration-causes-and-symptoms" target="_blank" rel="noopener noreferrer">dehydration</a>. But <a href="https://drinklmnt.com/blogs/health/can-you-drink-too-much-water" target="_blank" rel="noopener noreferrer">overhydration</a> with plain water can also have huge downsides: it exacerbates the low sodium levels (hyponatremia) endemic to the disorder. In other words, it dilutes the level of sodium in your blood, making the original problem worse.Depending on the genes affected, some patients also <a href="https://www.ncbi.nlm.nih.gov/books/NBK442019/" target="_blank" rel="noopener noreferrer">present</a> with excess urinary calcium. This can lead to kidney stones, blood in the urine, fever, vomiting, and calcification of the kidneys.Probably the most disturbing symptoms of Bartter syndrome are the symptoms surrounding birth, growth, and development. These include:<ul><li style="font-weight: 400">Intrauterine growth retardation (stunted growth before birth)</li><li style="font-weight: 400">Polyhydramnios (excessive amniotic fluid in the uterus driven by fetal polyuria)</li><li style="font-weight: 400">Stunted growth during early life</li><li style="font-weight: 400">Emaciation</li><li style="font-weight: 400">Sensorineural deafness (hearing loss)</li><li style="font-weight: 400">Drooping mouth</li><li style="font-weight: 400">Strabismus (crossed eyes)</li></ul>Let’s talk about the genes that cause Bartter syndrome now.<h2>What Causes Bartter Syndrome?</h2>Bartter syndrome is caused by <a href="https://www.ncbi.nlm.nih.gov/books/NBK442019/" target="_blank" rel="noopener noreferrer">mutations</a> in various genes governing electrolyte absorption. Usually, these mutations are in the NKCC2 and ROMK genes.The NKCC2 gene encodes for the sodium-chloride-potassium cotransporter in the kidneys. Mutations in this gene cause Type 1 Bartter syndrome.The ROMK gene encodes for potassium transport in the kidneys. Mutations in this gene cause Type 2 Bartter syndrome.Other genes are implicated in the other types of Bartter syndrome:<ul><li style="font-weight: 400">Type 3 Bartter syndrome is caused by mutations in CLC-Kb, a gene governing chloride absorption.</li><li style="font-weight: 400">Type 4a Bartter syndrome is caused by mutations in BSND, a gene that codes for a protein called bartinn that regulates electrolyte absorption in the kidneys.</li><li style="font-weight: 400">Type 4b Bartter syndrome is caused by mutations in the CLC-Ka and CLC-Kb genes that code for chloride absorption.</li><li style="font-weight: 400">Type 5 Bartter syndrome is caused by mutations in CASR, a gene that codes for the calcium-sensing receptor. (Note: Type 5 Bartter presents differently than types 1-4—with low serum calcium and high urinary calcium—so it doesn’t fit neatly into the more general discussion that follows.)</li></ul>The result of these genetic mutations is that the kidneys struggle to absorb sodium and chloride properly. As a consequence, too much <a href="https://drinklmnt.com/blogs/health/is-sodium-good-or-bad-for-you" target="_blank" rel="noopener noreferrer">sodium</a>, chloride, and fluids are lost through urine.As salt and body water drop away, blood volume drops too. And when blood volume drops, it <a href="https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6233707/" target="_blank" rel="noopener noreferrer">activates</a> the renin-angiotensin-aldosterone system.This trio of hormones is built for sodium retention, but it has an unfortunate side effect: it makes you pee out potassium like a firehose. That’s why hypokalemia is a defining feature of Bartter syndrome.<h2>Who Does Bartter Syndrome Affect?</h2>Bartter syndrome only <a href="https://www.ncbi.nlm.nih.gov/books/NBK442019/" target="_blank" rel="noopener noreferrer">affects</a> about 1 in 1,000,000 people. It’s about 25 times less common than <a href="https://drinklmnt.com/blogs/health/gitelman-syndrome" target="_blank" rel="noopener noreferrer">Gitelman syndrome</a>, a similar disorder of diminished electrolyte absorption.In 1962, Dr. Frederic Bartter first <a href="https://rarediseases.org/rare-diseases/bartters-syndrome/" target="_blank" rel="noopener noreferrer">identified</a> the syndrome that now bears his name. He noticed that younger people were presenting with high levels of aldosterone, normal-to-low blood pressure, and growth retardation.Bartter syndrome may be at its most dangerous in the antenatal (pre-birth) period. Along with the <a href="http://drinklmnt.com/blogs/health/low-electrolytes-symptoms" target="_blank" rel="noopener noreferrer">symptoms of low electrolytes</a>, infants and children with Bartter syndrome also struggle with stunted growth, GI symptoms, and reduced quality of life in certain areas. The symptoms tend to improve with age.<h2>Diagnosing Bartter Syndrome</h2>To diagnose Bartter syndrome, a physician will review family history, symptoms, and a battery of lab work.Family history is important because Bartter syndrome is an inherited disorder. If both mother and father have copies of the problematic mutation, there’s a chance they’ll pass along the trait (Bartter syndrome) to their child.Since two copies of the mutation must be present to develop the condition, Bartter syndrome is called an autosomal recessive disorder. This explains why Bartter syndrome is so rare. Not just one—but both—parents must carry the mutation to pass it along.After reviewing family history, the next rung is symptomology. Are there symptoms of <a href="https://drinklmnt.com/blogs/health/how-to-prevent-an-electrolyte-imbalance-and-what-causes-them#:~:text=Low%20serum%20sodium%20is%20called,too%20much%20sodium%2Dfree%20water." target="_blank" rel="noopener noreferrer">low salt or low potassium</a>? Is there excessive urination, excessive thirst, and salt cravings? All these symptoms strengthen the case for Bartter syndrome.There’s a boatload of lab work that may confirm or disconfirm a diagnosis. Lab results that suggest Bartter syndrome <a href="https://www.ncbi.nlm.nih.gov/books/NBK442019/" target="_blank" rel="noopener noreferrer">include</a>:<ul><li style="font-weight: 400">Hypokalemia, hyponatremia, <a href="https://drinklmnt.com/blogs/health/hypercalcemia-and-hypocalcemia" target="_blank" rel="noopener noreferrer">hypocalcemia</a>—and (more rarely) hypomagnesemia and hypophosphatemia</li><li style="font-weight: 400">Metabolic alkalosis (blood PH above 7.5)</li><li style="font-weight: 400">Elevated aldosterone, renin, and angiotensin</li><li style="font-weight: 400">Elevated urinary sodium, chloride, potassium, and calcium (elevated urinary calcium, hypercalciuria, helps <a href="https://www.ncbi.nlm.nih.gov/books/NBK442019/" target="_blank" rel="noopener noreferrer">distinguish</a> Bartter from Gitelman syndrome.)</li><li style="font-weight: 400">Elevated urinary prostaglandins (prostaglandins are lipids crucial for immune function, but excess prostaglandins can disrupt kidney function)</li><li style="font-weight: 400">Large amounts of amniotic fluid or stunted growth as seen via ultrasound</li></ul>Finally, to confirm the diagnosis—and to identify the type of Bartter in question—it makes sense to follow up with genetic testing. This is relatively inexpensive considering its importance. You can sequence your genome for around $100, then run it through a genetic database like <a href="https://promethease.com/" target="_blank" rel="noopener noreferrer">Promethease</a> to check for the relevant mutations.<h2>Treating Bartter Syndrome</h2>There is no cure for Bartter syndrome. It’s a genetic disorder, and we don’t yet have the genetic therapies to prevent or reverse it.Treating Bartter syndrome is mostly a matter of managing fluid and electrolyte intake. Specifically, the program should prioritize getting plenty of <a href="https://science.drinklmnt.com/electrolytes/does-salt-help-with-hydration/" target="_blank" rel="noopener noreferrer">salt</a>, potassium, and water.Other treatments <a href="https://www.ncbi.nlm.nih.gov/books/NBK442019/" target="_blank" rel="noopener noreferrer">include</a>:<ul><li style="font-weight: 400">NSAIDs (to reduce excessive prostaglandins, which aggravate electrolyte disturbances)</li><li style="font-weight: 400">Potassium-sparing diuretics</li><li style="font-weight: 400">ACE inhibitors</li></ul>These treatments, unfortunately, come with undesirable side effects. NSAIDs, for instance, are <a href="https://www.ncbi.nlm.nih.gov/books/NBK547742/" target="_blank" rel="noopener noreferrer">well-documented</a> to increase the risk of heart attack, blood clots, and atrial fibrillation.It’s important that you consult with your medical professional on all treatments. Still, if you have data to show you’re consistently low on electrolytes, a good place to start is with an <a href="https://drinklmnt.com/blogs/health/electrolyte-rich-foods-and-when-to-supplement" target="_blank" rel="noopener noreferrer">electrolyte-rich diet</a>. That means consuming magnesium, calcium, and potassium-rich foods like leafy greens, cruciferous vegetables, meat, avocados, and starchy tubers.It also means shaking the salt shaker like a shake weight. Most people need more salt anyways, and that’s doubly true for folks with Bartter syndrome. My baseline recommendation is 2.5 teaspoons of salt per day. And because they can’t absorb salt properly, those with Bartter syndrome will likely need more.Potassium supplementation may also be warranted. If so, potassium chloride is the best choice for those with Bartter syndrome because it supplies both potassium and chloride.They’ll also probably need more fluids. While drinking to thirst is generally effective for preventing dehydration, large urinary losses may require a more aggressive hydration strategy. But remember: when drinking beyond thirst, the trick is to hydrate with water PLUS electrolytes. This will prevent sodium, potassium, and magnesium levels from falling, and in turn, prevent low electrolytes symptoms.I teamed up with my coaches to create <a href="https://drinklmnt.com/products/lmnt-recharge-electrolyte-drink" target="_blank" rel="noopener noreferrer">LMNT</a> for that reason. It’s a tasty electrolyte drink mix that helps maintain bodily fluids and electrolytes while you hydrate. It contains 1000 mg sodium, 200 mg potassium, 60 mg magnesium, and 0 sugar. I believe it could help folks with Bartter syndrome.One last note. If you know someone with Bartter syndrome—or if it runs in their family—please forward them this article. Beyond scientific papers, there aren’t many resources on this rare genetic disorder. The info could make a big difference in their quality of life.