OVERVIEW

What is Bartter Syndrome?

Bartter syndrome, translated as Bartter syndrome in Chinese, is a rare autosomal recessive genetic disorder. It often manifests in childhood, with primary symptoms including growth retardation, hypokalemia, metabolic alkalosis, polyuria, and polydipsia. It may also present with elevated urinary calcium, mild hypermagnesemia, and no hypertension.

Currently, Bartter syndrome is believed to be associated with congenital genetic defects leading to dysfunction in renal tubular reabsorption.

For patients with unexplained hypokalemia, metabolic alkalosis, elevated renin and aldosterone levels but no hypertension, Bartter syndrome should be considered after excluding common causes. However, a definitive diagnosis requires genetic testing to confirm the presence of gene mutations.

Bartter syndrome requires lifelong medication to correct electrolyte imbalances and mitigate the adverse effects of elevated renin, aldosterone, and prostaglandins on the body.

SYMPTOMS

What are the manifestations of Bartter syndrome?

Bartter syndrome usually manifests in childhood, with the following main symptoms:

• Delayed physical and mental development;
• Hypokalemia, specifically manifested as fatigue, easy exhaustion, muscle weakness, possible lower limb paralysis, and even difficulty swallowing or breathing, often accompanied by metabolic alkalosis;
• Hypokalemia-induced arrhythmia, specifically manifested as palpitations, tachycardia, and irregular heartbeat;
• Abnormal urine concentration function, specifically manifested as increased urine output, excessive thirst, and high water intake;
• Normal or low blood pressure;
• Normal or low blood magnesium levels;
• Possible increased urinary calcium excretion.

In fact, depending on the genetic defect, Bartter syndrome can be further divided into types I, II, III, IV, and V, with slightly different manifestations for each type.

• Types I and II: These are more severe. Affected children show abnormalities before birth, which can lead to polyhydramnios during pregnancy and premature birth, possibly resulting in stillbirth or neonatal death.
• Type III: The most common and less severe form, typically manifesting at an older age.
• Type IV: Also severe, with fetal abnormalities, including stillbirth. Surviving children often have hearing loss.
• Type V: Less severe, with late onset, often accompanied by hypocalcemia and hypomagnesemia.

What diseases can Bartter syndrome cause?

• Proteinuria
• Impaired kidney function
• Nephrogenic diabetes insipidus

CAUSES

What is the cause of Bartter syndrome?

Genetic defects impair the transporters involved in sodium chloride reabsorption in the loop of Henle in the kidneys.

Simply put, genetic defects damage certain kidney functions. These defective genes are inherited from both parents, who may not necessarily have Bartter syndrome themselves.

Is Bartter syndrome hereditary?

Yes.

Bartter syndrome is an autosomal recessive genetic disorder. If one parent has the disease and the other carries the pathogenic gene, their child may develop the condition or carry the gene.

DIAGNOSIS

What tests are needed to diagnose Bartter syndrome?

• Blood tests: Check electrolytes, blood gas analysis, renin, aldosterone, etc. Patients with Bartter syndrome will have low blood potassium, normal or low blood magnesium, normal or low blood phosphorus, metabolic alkalosis, and elevated renin and aldosterone.

• Urine tests: Collect a single morning urine sample and a 24-hour urine sample. Patients with Bartter syndrome will have low urine specific gravity, increased 24-hour urine volume, elevated 24-hour urine potassium, and normal or high 24-hour urine calcium.

• Genetic testing: Although genetic testing can confirm Bartter syndrome, it is rarely used due to its complexity and high cost. In practice, doctors can usually diagnose Bartter syndrome by reviewing medical history, examining blood and urine tests, and ruling out other causes of hypokalemia, without necessarily requiring genetic testing.

What diseases or conditions have similar symptoms to Bartter syndrome?

• Diuretic side effects: Improper use of diuretics can cause hypokalemia and other symptoms, which usually improve after discontinuation.
• Self-induced vomiting: This is often done secretly, and patients may hide it from doctors. However, long-term self-induced vomiting is often accompanied by scars on the back of the hand (from inserting into the mouth), teeth erosion due to stomach acid, and parotitis. The absence of these features does not rule out self-induced vomiting. Measuring urine chloride can help distinguish it from Bartter syndrome—low in self-induced vomiting and high in Bartter syndrome.
• Gitelman syndrome: Gitelman syndrome is also an autosomal recessive disorder, characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and normal blood pressure. It is diagnosed later than Bartter syndrome, typically in late childhood or adulthood. Measuring urine calcium can differentiate the two—normal or high in Bartter syndrome and low in Gitelman syndrome.
• Aminoglycoside antibiotic side effects: Representative drugs include gentamicin and amikacin. Side effects include hypokalemia, metabolic alkalosis, hypomagnesemia, and hypercalciuria, which usually resolve within 2–6 weeks after discontinuation.
• EAST syndrome: EAST syndrome is a rare genetic disorder that appears in infancy, with symptoms including epilepsy, ataxia, deafness, hypokalemia, metabolic alkalosis, and normal blood pressure.

TREATMENT

Which department should I visit for Bartter syndrome?

Endocrinology, Nephrology.

Is it necessary to seek medical attention for Bartter syndrome?

Yes, it is mandatory.

The hypokalemia caused by Bartter syndrome can lead not only to limb weakness and paralysis but also to arrhythmias, which may result in sudden death in severe cases. Therefore, once hypokalemia is detected, immediate medical attention is crucial.

How is Bartter syndrome treated?

• NSAIDs + Potassium-sparing diuretics: NSAIDs include aspirin, indomethacin, etc.; potassium-sparing diuretics include spironolactone, amiloride, etc.
• Angiotensin inhibitors: These are adjunctive medications for Bartter syndrome, commonly named "XX-pril," such as enalapril. Not all patients require angiotensin inhibitors.
• Potassium supplementation: With NSAIDs and potassium-sparing diuretics, a small number of patients may normalize their potassium levels. For those who remain hypokalemic, potassium supplementation (e.g., oral potassium chloride tablets) can be added. Type V Bartter syndrome patients also require magnesium supplementation.
• Kidney transplantation: Medical reports on kidney transplantation are scarce due to the rarity of Bartter syndrome. Currently, transplantation is only considered for patients with end-stage renal disease.
• Treatment for polyhydramnios during pregnancy: Types I, II, and IV Bartter syndrome are severe forms, with fetal abnormalities detectable prenatally, leading to polyhydramnios and preterm birth. If polyhydramnios occurs without a clear cause, fetal Bartter syndrome should be considered. Testing amniotic fluid chloride levels can aid diagnosis—elevated levels suggest Bartter syndrome or congenital chloride diarrhea. Severe polyhydramnios may be treated with NSAIDs for the mother until 31 weeks of gestation.

What are the common side effects of Bartter syndrome medications?

• NSAIDs: Stomach discomfort, gastritis, peptic ulcers, gastrointestinal bleeding, kidney dysfunction.
• Spironolactone: Erectile dysfunction, decreased libido, gynecomastia in males, menstrual irregularities in females.
• Amiloride: Headache, fatigue, erectile dysfunction, gastrointestinal discomfort, hyperuricemia.
• Angiotensin inhibitors: Dry cough, hypotension.
• Potassium chloride: Nausea, vomiting, throat irritation, chest pain, abdominal pain, diarrhea, peptic ulcers, and bleeding. Magnesium supplements: Diarrhea.

Is hospitalization required for Bartter syndrome? What should be noted during hospitalization?

Yes. The purpose of hospitalization is to complete diagnostic tests, confirm the diagnosis, and establish an appropriate treatment plan. Follow-ups can later be managed outpatient.

During hospitalization, 24-hour urine collection may be required. Patients should avoid leaving the ward during this period. If tests are necessary outside the ward, a urine container must be carried to collect all urine. Adequate water intake is advised to ensure sufficient urine volume.

Can Bartter syndrome be completely cured?

No.

Bartter syndrome cannot be cured but can be managed with medications to correct symptoms like hypokalemia, requiring lifelong treatment.

Can Bartter syndrome lead to death?

Yes, it can.

Types I, II, and IV Bartter syndrome are severe forms, with fetal abnormalities detectable prenatally, potentially causing intrauterine fetal death or neonatal death.

Additionally, the primary manifestation of Bartter syndrome is hypokalemia, which can lead to arrhythmias, cardiac arrest, and sudden death.

DIET & LIFESTYLE

What should be paid attention to in daily life with Bartter syndrome?

• Take medication on time, do not stop taking it arbitrarily, and go to the hospital for regular check-ups as directed by the doctor.
• Symptoms such as fatigue and palpitations may indicate low blood potassium levels, and medical attention should be sought promptly.

Does Bartter syndrome affect fertility?

Yes.

Both Bartter syndrome itself and the medications used to treat it may affect fertility. Patients with Bartter syndrome who plan to have children are advised to discuss this thoroughly with their doctor in advance.

What dietary precautions should be taken with Bartter syndrome?

• There are no specific dietary restrictions; a healthy and balanced diet is sufficient.

• When cooking, use less salt, less oil, and fewer high-salt seasonings. Avoid pickled vegetables and meats.

• Do not rely solely on refined grains like white rice and flour. Substitute part of the staple food with whole grains, legumes, potatoes, or pumpkin.

• Balance meat and vegetable intake. Prefer white meats such as chicken, duck, and fish, and limit fatty meats. Eggs and milk are important sources of protein and other nutrients.

• Vegetarians can consume more beans and bean products to supplement protein.

• Eat plenty of fruits and vegetables.

• Avoid alcohol as much as possible.

PREVENTION

Can Bartter Syndrome Be Prevented?

There is currently no way to prevent it. Bartter syndrome patients with fertility needs can seek genetic counseling at relevant institutions.