From the Guidelines
Bartter syndrome is indeed hereditary, and testing for it typically involves genetic analysis to confirm the clinical diagnosis, which is recommended whenever possible 1.
Diagnosis and Testing
The diagnosis of Bartter syndrome (BS) should be considered in the presence of renal salt wasting, polyuria, rapid weight loss, and signs of dehydration, especially in the postnatal period 1.
- Evaluation of medical history, including polyhydramnios, premature birth, growth failure, and family history, is essential.
- Biochemical parameters such as serum electrolytes, acid-base status, renin, aldosterone, creatinine, fractional excretion of chloride, and urinary calcium-creatinine ratio should be assessed.
- Renal ultrasound to detect medullary nephrocalcinosis and/or kidney stones is also recommended.
Genetic Analysis and Counseling
Genetic analysis is crucial for confirming the diagnosis of BS, and it is recommended to offer genetic counseling for families with probands with confirmed clinical and/or genetic diagnosis of BS 1.
- The mode of inheritance is autosomal recessive in most types of BS, except for type 5, which is X-linked recessive 1.
- Genetic counseling can help families understand the risk of passing the mutated gene to their offspring and allow for early diagnosis and management.
Management and Treatment
While the focus of the question is on testing, it's essential to note that management of BS typically involves supplementation with sodium chloride, potassium chloride, and fluids, as well as nonsteroidal anti-inflammatory drugs (NSAIDs) in most patients, at least during the first years of life 1.
- The use of other therapies, such as potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, may be considered, but evidence supporting their efficacy is limited 1.
From the Research
Bartter's Syndrome Overview
- Bartter's syndrome is an inherited renal tubular disorder caused by a defective salt reabsorption in the thick ascending limb of the loop of Henle, resulting in salt wasting, hypokalemia, and metabolic alkalosis 2.
- The syndrome is characterized by renal salt wasting, lowered blood pressure, hypokalemic metabolic alkalosis, and hypercalciuria with a variable risk of renal stones 3.
Genetic Causes
- Mutations of several genes encoding the transporters and channels involved in salt reabsorption in the thick ascending limb cause different types of Bartter syndrome 2.
- Five genes have been identified as causing Bartter syndrome (types I-V), with the unifying pathophysiology being the loss of salt transport by the thick ascending limb 3.
- BS types I, II, and III are caused by mutations on genes encoding the luminal Na+-K+-2Cl- co-transporter, the luminal K+ channel ROMK, and the basolateral chloride channel ClC-Kb (CLCNKB), respectively 4.
Diagnosis and Treatment
- Phenotypic identification still remains the first step to guide the suspicion of Bartter syndrome 2.
- Treatment focuses mainly on correcting dehydration and electrolyte disturbances and in measures to reduce polyuria, including the use of nonsteroidal anti-inflammatory medications to control excessive renal prostaglandin E2 production 4.
- Early diagnosis and treatment of BS may prevent long-term consequences such as growth failure, nephrocalcinosis, and end-stage renal disease 4.
Hereditary Aspects
- Bartter's syndrome is a group of autosomal recessive disorders 3.
- The syndrome can be classified into antenatal and classic BS, with different subtypes caused by mutations in different genes 4.
- Loss-of-function mutations of Barttin CLCNK type accessory beta subunit cause BS type IVa, and simultaneous mutations of CLCNKB and CLCNKA cause BS type IVb 4.