Bartter disease type 3

Bartter Syndrome Type 3: A Rare Genetic Disorder

Bartter syndrome type 3 (BS3) is a rare autosomal recessive genetic disorder that affects the kidneys' ability to reabsorb salt and electrolytes. This condition is characterized by a range of symptoms, including:

• Polyuria: Frequent urination due to excessive urine production
• Hypokalemia: Low potassium levels in the blood
• Hypochloremia: Low chloride levels in the blood
• Metabolic alkalosis: A condition where the body's pH level becomes too high

BS3 is caused by mutations of the chloride voltage-gated channel Kb gene, which plays a crucial role in salt reabsorption in the kidneys. This genetic defect leads to impaired salt reabsorption in the thick ascending loop of Henle, resulting in excessive loss of electrolytes and water.

Clinical Features

The clinical features of BS3 can vary widely among affected individuals. Some common symptoms include:

• Hypokalemia: Low potassium levels can lead to muscle weakness, fatigue, and heart problems
• Metabolic alkalosis: This condition can cause confusion, dizziness, and other neurological symptoms
• Polyuria: Frequent urination can disrupt sleep patterns and daily activities

Comparison with Other Bartter Syndromes

BS3 is distinct from other types of Bartter syndrome, such as classic Bartter syndrome (CBS) and neonatal/antenatal Bartter syndrome. While CBS presents with a milder clinical picture than BS3, neonatal/antenatal Bartter syndrome is characterized by more severe symptoms, including sensorineural deafness.

References

• [1] Seys E. (2017). Bartter syndrome type 3: A clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene. [Cited by 133]
• [6] Liu J. (2023). Background: Bartter syndrome (BS) type III is a rare autosomal recessive genetic disease. Its clinical features are polyuria, hypokalemia, hypochloremia, metabolic alkalosis... [Cited by 1]
• [8] Bartter syndrome, type 3 is a group of disorders with autosomal recessive transmission causing impaired salt reabsorption in the thick ascending loop of Henle.

Bartter syndrome type 3, also known as classic Bartter syndrome, is characterized by a range of symptoms that can vary in severity.

Common signs and symptoms include:

• Low levels of potassium in the blood (hypokalemia), which can result in muscle weakness, cramping, and fatigue [2].
• Dehydration, fatigue, cramping, weakness, brittle bones, and other electrolyte abnormalities [3].
• Muscle weakness and cramping due to electrolyte imbalances [6].
• Repeated vomiting, muscle spasms, cramp, persistent thirst, and frequent need to urinate [7].

Severe symptoms may include:

• Polyhydramnios (excessive amniotic fluid) and premature birth in newborns.
• Excessive urination (polyuria), fever, dehydration, and other complications.

It's worth noting that the severity of symptoms can vary depending on the genotype and individual factors. If you have any specific questions or would like more information, feel free to ask!

References: [1] Not applicable [2] 2. Feb 1, 2011 — Bartter syndrome is also characterized by low levels of potassium in the blood (hypokalemia), which can result in muscle weakness, cramping, and ... [3] 3. Apr 23, 2024 — Also known as salt-wasting nephropathy, Bartter syndrome is characterized by dehydration, fatigue, cramping, weakness, brittle bones, and ... [6] 6. Manifestations vary depending on genotype, but growth and development may be affected and electrolyte abnormalities may cause muscle weakness, cramping, spasms, ... [7] 7. What are the signs and symptoms of Bartter syndrome? · repeated vomiting · muscle weakness · muscle spasms · cramp · persistent thirst · frequent need to urinate ...

Bartter syndrome, specifically type 3, can be diagnosed through various diagnostic tests.

Clinical Diagnosis

Diagnosis of Bartter syndrome is primarily based on clinical presentation and laboratory findings [1]. The condition is characterized by an imbalance of electrolytes in the body, including potassium, sodium, chloride, and bicarbonate [7].

Laboratory Tests

The diagnosis involves measuring serum and urinary electrolyte levels, which can help confirm the presence of Bartter syndrome [8]. These tests typically include:

• Serum and urinary electrolyte measurement (sodium, potassium, chloride, bicarbonate)
• Blood gas analysis
• Plasma and urine electrolytes (magnesium, calcium)

Genetic Testing

Genetic testing is also available to confirm the diagnosis of Bartter syndrome [6]. This can be done through CLCNKB testing, which is UKGTN-approved, and may be requested by consultants via forms available online. Genetic testing can help identify the specific genetic mutation responsible for the condition.

Prenatal Diagnosis

In cases where there is a family history of Bartter syndrome or if the mother has symptoms during pregnancy, prenatal diagnosis can be performed [3]. This involves ultrasonography to detect polyhydramnios and intrauterine growth restriction. Genetic testing of amniotic fluid can also confirm the presence of the condition.

References

[1] Context 1 [2] Context 6 [3] Context 3 [4] Context 8 [5] Context 10

Bartter syndrome, including type 3, is a rare genetic disorder that affects the kidneys' ability to regulate electrolytes and water balance in the body. The treatment for Bartter syndrome typically involves managing symptoms and correcting electrolyte imbalances.

Medications Used:

• Potassium supplements are often prescribed to help correct low potassium levels (hypokalemia) [1].
• Diuretics, specifically potassium-sparing diuretics, may be used to help manage high blood pressure and prevent further electrolyte imbalances [2].
• ACE inhibitors can also be used to control blood pressure and improve kidney function [3].
• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin or ibuprofen, may be considered for the management of patients with Bartter syndrome, especially in early childhood [4][5].

Treatment Goals:

The primary goal of treatment is to correct electrolyte imbalances and manage symptoms. This can involve a combination of medications, dietary changes, and lifestyle modifications.

• Oral salt and potassium supplements are often recommended to help replenish lost electrolytes [6].
• Liberal salt and fluid intake may also be advised to help maintain proper hydration levels [7].

Recommendations:

Recent studies have suggested that treatment with NSAIDs, such as ibuprofen, can be beneficial in symptomatic patients with Bartter syndrome, especially in early childhood [8]. Comprehensive therapy with a combination of medications, including ibuprofen, antisterone, captopril, and potassium supplements, has been shown to have remarkable effects on growth retardation and other symptoms [9].

References:

[1] Context 1 [2] Context 2 [3] Context 3 [4] Context 5 [5] Context 8 [6] Context 6 [7] Context 7 [8] Context 8 [9] Context 9

Bartter disease type 3 (BS3) can be challenging to diagnose due to its phenotypic overlap with other conditions. Here are some key points to consider for differential diagnosis:

• Gitelman syndrome: BS3 and Gitelman syndrome share similar clinical features, including hypokalemia, metabolic alkalosis, and hypomagnesemia [5]. In fact, several patients with BS3 have been reported to have clinical features that are virtually indistinguishable from Gitelman syndrome [9].
• Pseudo-Bartter/Gitelman syndrome: The phenotypic overlap between BS3, Gitelman syndrome, and pseudo-Bartter/Gitelman syndrome (p-BS/GS) can make differential diagnosis difficult. Pseudo-BS/GS is a condition that presents with similar clinical features to BS3 and Gitelman syndrome but lacks the genetic mutations associated with these conditions [2][3].
• Antenatal Bartter syndrome: In cases of antenatal Bartter syndrome, fetal megabladder may be a distinguishing feature from other forms of BS3. However, this can only be confirmed through prenatal ultrasound or other diagnostic tests [8].

To differentiate between these conditions, clinicians should consider the following:

• Genetic testing: Genetic analysis is essential to confirm the diagnosis of BS3 and distinguish it from Gitelman syndrome and pseudo-BS/GS.
• Clinical presentation: A thorough clinical evaluation, including assessment of electrolyte levels, renal function, and other relevant parameters, can help differentiate between these conditions.
• Family history: A detailed family history may provide clues to the underlying genetic cause of the condition.

In summary, differential diagnosis of BS3 requires a comprehensive approach that takes into account the phenotypic overlap with other conditions. Genetic testing, clinical presentation, and family history are all important factors to consider in making an accurate diagnosis.

References:

[1] Kleta, R. [2] by N Matsunoshita · 2016 · Cited by 106 — [3] by N Matsunoshita · 2016 · Cited by 106 — [5] by T da Silva Cunha · 2018 · Cited by 159 — [8] by OF Bamgbola · 2021 · Cited by 10 — [9] by M Konrad · 2021 · Cited by 125 —