From the Guidelines
Bartter syndrome is classified into five main types based on genetic mutations and clinical features, with each type presenting with varying severity of hypokalemia, metabolic alkalosis, and increased urinary excretion of sodium, potassium, and chloride, as reported in the most recent study by 1.
Types of Bartter Syndrome
The five types of Bartter syndrome are:
- Type I: caused by mutations in the SLC12A1 gene affecting the sodium-potassium-chloride cotransporter
- Type II: involves mutations in the KCNJ1 gene affecting potassium channels
- Type III: results from mutations in the CLCNKB gene affecting chloride channels
- Type IV: characterized by mutations in either the BSND gene or both CLCNKA and CLCNKB genes, often causing sensorineural deafness along with renal symptoms
- Type V: the rarest form, involves mutations in the CASR gene that regulates calcium sensing
Clinical Features and Treatment
Each type presents with varying severity of the classic symptoms, including hypokalemia, metabolic alkalosis, normal blood pressure despite elevated renin and aldosterone levels, and increased urinary excretion of sodium, potassium, and chloride, as described in 1. The age of onset differs among types, with Types I and II typically manifesting prenatally or in early infancy, Type III appearing in childhood, Type IV presenting at birth with additional hearing impairment, and Type V showing hypocalcemia alongside the typical features. Treatment generally includes potassium supplementation, prostaglandin inhibitors like indomethacin, and potassium-sparing diuretics, with specific approaches tailored to each type's unique characteristics.
Key Considerations
It is essential to distinguish Bartter syndrome from other salt-losing tubulopathies and to consider the potential risks and benefits of prenatal intervention, as discussed in 1. Genetic testing is crucial for diagnosis, and a minimal diagnostic panel should include genes underlying Bartter syndrome, as well as Gitelman syndrome, which can be difficult to distinguish clinically from BS3, as recommended in 1.
From the Research
Types of Bartter Syndrome
Bartter syndrome can be classified into different types based on the underlying mutant gene and clinical presentation. The main types of Bartter syndrome are:
- Antenatal or neonatal Bartter syndrome (aBS)
- Classic Bartter syndrome (cBS)
- Five subtypes based on the underlying mutant gene:
Clinical Presentation
The clinical presentation of Bartter syndrome can vary depending on the type and underlying gene mutation. Some common features include:
- Renal salt wasting
- Hypokalemic metabolic alkalosis
- Hypercalciuria
- Hyperreninaemic hyperaldosteronism
- Nephrocalcinosis
- Sensorineural deafness (in some types, such as Type IV) 5, 6
- Growth failure 3
- Prematurity (in antenatal Bartter syndrome) 3
Genotype-Phenotype Correlation
The genotype-phenotype correlation in Bartter syndrome is not always clear-cut, and patients with the same gene mutation can present with different phenotypes 2, 3. However, some studies have identified specific mutations and their corresponding clinical features, which can aid in diagnosis and genetic counseling 3, 6.