Barth syndrome

Barth Syndrome: A Rare Genetic Disorder

Barth syndrome, also known as BTHS, is a rare genetic disorder that affects the heart, immune system, muscles, and growth in males. It is characterized by a combination of symptoms, including:

• Cardiomyopathy: An enlarged and weakened heart (dilated cardiomyopathy) [8][9]
• Neutropenia: Recurrent infections due to small numbers of white blood cells [3][7]
• Skeletal myopathy: Weakness in muscles used for movement [13][14]
• Growth delay: Short stature and prepubertal growth delay [4][5]

Barth syndrome is caused by genetic changes in the TAZ gene, which is inherited in an X-linked recessive manner. This means that it primarily affects males, as they have only one X chromosome [4].

The symptoms of Barth syndrome can vary in severity and may not be present at birth or shortly afterward. Children with Barth syndrome usually have a shorter lifespan due to heart issues, but treatments can lower the risk of complications and maximize quality of life [1][2].

It's essential to note that Barth syndrome is a rare condition, and its diagnosis can be challenging due to the complexity of its symptoms. A diagnosis should be considered for a child or adult presenting with any one of its eight cardinal characteristics and in cases with family histories of multiple male deaths or other related conditions [3].

Barth Syndrome Signs and Symptoms

Barth syndrome, also known as 3-methylglutaconic aciduria (3-MGA), is a rare genetic condition that affects boys. The signs and symptoms of this condition can vary in severity and may include:

• Enlarged and weakened heart: Barth syndrome often leads to an enlarged and weakened heart, which can cause problems with the heart's ability to pump blood effectively [1].
• Muscle weakness: Affected individuals may experience muscle weakness, particularly in the muscles used for movement (skeletal muscles) [1].
• Low blood cell count: People with Barth syndrome often have a low blood cell count, which can lead to fatigue and other complications [3].
• Fatigue: Fatigue is a common symptom of Barth syndrome, as the body struggles to produce enough energy due to the condition's effects on the heart and muscles [6][8].
• Distinct facial features: Some individuals with Barth syndrome may have distinct facial features, including prominent ears, cheekbones, and deep-set eyes [5].
• Low blood sugar: People with Barth syndrome should be aware of the signs of low blood sugar, such as excessive weakness, change in pallor, and excessive sweating [6].
• Lactic acidosis and mild anemia: Affected boys may experience lactic acidosis and mild anemia, which can further exacerbate fatigue and other symptoms [9].

It's essential to note that the severity and presentation of Barth syndrome can vary significantly from person to person. If you or someone you know is experiencing these symptoms, it's crucial to consult with a medical professional for proper diagnosis and treatment.

References: [1] - Context result 1 [2] - Context result 2 [3] - Context result 3 [5] - Context result 5 [6] - Context result 6 [8] - Context result 8 [9] - Context result 9

Barth syndrome, also known as 3-methylglutaconic aciduria, is a rare genetic disorder that affects males. Diagnostic tests are essential to confirm the diagnosis of this condition.

Laboratory Tests

Several laboratory tests can be undertaken to confirm the diagnosis of Barth syndrome:

• Finding a tafazzin gene (TAZ) mutation [1]
• Routine cardiolipin testing in all young males with dilated cardiomyopathy (DCM) [2]
• Urine or blood tests to check for signs of the condition, such as elevated excretion of organic acids (typically 3-methylglutaconic acid (3-MGCA)) [4] and increased levels of chemicals like 3-methyglutaconic acid and 2-ethyl hydracrylic acid in the urine or blood [6]
• Analysis of the ratio of monolysocardiolipin (MLCL) / cardiolipin (CL) on blood, tissue, fibroblasts or stored neonatal bloodspots [7]

Genetic Testing

Testing is performed by sequencing of the entire coding region of the TAZ gene. This will detect point mutations, small deletions and small insertions [9]. The Barth Service in Bristol, England recommends routine cardiolipin testing in all young males with dilated cardiomyopathy (DCM) [2].

Other Diagnostic Features

Most males with Barth syndrome have neutropenia, which is characterized by consistently low levels of white blood cells [8]. Additionally, affected individuals may exhibit cardiomyopathy, skeletal myopathy, prepubertal growth delay, and distinctive facial gestalt [4].

In conclusion, diagnostic tests for Barth syndrome include laboratory tests such as cardiolipin testing, urine or blood tests to check for signs of the condition, genetic testing by sequencing of the TAZ gene, and analysis of the ratio of MLCL / CL. Other diagnostic features include neutropenia, cardiomyopathy, skeletal myopathy, prepubertal growth delay, and distinctive facial gestalt.

References: [1] Context 1 [2] Context 2 [4] Context 4 [6] Context 6 [7] Context 7 [8] Context 8 [9] Context 9

Current Status of Drug Treatment for Barth Syndrome

Barth syndrome, also known as 3-methylglutaconic aciduria, is a rare genetic disorder that affects the heart and other organs. While there is no cure or specific treatment for the condition, researchers have been exploring various drug treatments to manage its symptoms.

Elamipretide: A Promising Candidate

One of the most promising candidates in this regard is elamipretide, a mitochondrial-targeting peptide that has shown potential in treating heart failure and Barth syndrome. According to search results [1], elamipretide was the first drug with the potential to treat mitochondria in heart failure and by extension in Barth syndrome.

Previous Studies on Bezafibrate

Previous mechanistic studies have identified bezafibrate, a lipid-lowering drug, as a promising potential treatment for Barth syndrome [2]. However, no human trials have been conducted to date to confirm its efficacy.

Current Treatment Focuses on Symptom Management

Currently, the focus of treatment for Barth syndrome is on reducing symptoms and preventing complications. There are currently no FDA- or EMA-approved therapies for patients with Barth syndrome [3].

Elamipretide's Regulatory Status

However, elamipretide has received significant attention in recent years. The Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for elamipretide for the treatment of Barth syndrome [4]. Additionally, the Cardiovascular and Renal Drugs Advisory Committee voted 10-6 supporting Stealth Biotherapeutics' elamipretide for treating Barth syndrome [5].

Conclusion

In conclusion, while there is no cure or specific treatment for Barth syndrome, researchers are actively exploring various drug treatments to manage its symptoms. Elamipretide appears to be a promising candidate in this regard, with significant regulatory attention and support.

References:

[1] Search result 1: Nov 8, 2023 — Elamipretide was the first drug with the potential to treat mitochondria in heart failure and by extension in Barth syndrome. [2] Search result 4: May 31, 2021 — Previous mechanistic studies have identified the lipid-lowering drug bezafibrate as a promising potential treatment; however, to date, no human ... [3] Search result 5: How is Barth syndrome treated? There is no cure or specific treatment for Barth syndrome. Treatment focuses on reducing symptoms and preventing complications. [4] Search result 8: Apr 8, 2024 — The Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for elamipretide for the treatment of Barth syndrome. [5] Search result 7: Oct 10, 2024 — The Cardiovascular and Renal Drugs Advisory Committee voted 10-6 supporting Stealth Biotherapeutics' elamipretide for treating Barth syndrome.

Differential Diagnosis of Barth Syndrome

Barth syndrome, also known as 3-methylglutaconic aciduria (3-MGA), is a rare genetic disorder that affects males. When diagnosing Barth syndrome, it's essential to consider the differential diagnoses, which are conditions that have similar symptoms and must be ruled out before making an accurate diagnosis.

Conditions to Consider

• Hereditary cardiomyopathies: These include conditions such as dilated cardiomyopathy, hypertrophic cardiomyopathy, and noncompaction of the left ventricle. [2][3]
• Nutritional cardiomyopathies: Malnutrition or other nutritional deficiencies can lead to cardiomyopathy, which must be ruled out in patients with Barth syndrome. [4]
• Idiopathic/cyclic neutropenia: This condition is characterized by recurring episodes of low white blood cell count and can mimic the symptoms of Barth syndrome. [4]
• Metabolic and viral cardiomyopathies: These conditions can cause similar heart problems to those seen in Barth syndrome, making them important differential diagnoses. [5][6]
• Mitochondrial diseases: Certain mitochondrial disorders can present with similar symptoms to Barth syndrome, including cardiomyopathy and neutropenia. [5]

Key Points

• Differential diagnosis is crucial for accurate diagnosis of Barth syndrome.
• Conditions that increase 3-MGA levels must be excluded before diagnosing Barth syndrome. [3][7]
• Cardiolipin ratio testing can help diagnose Barth syndrome, but differential diagnoses must still be considered. [9]

References:

[1] Oct 9, 2014 — Barth syndrome is characterized in affected males by cardiomyopathy, neutropenia, skeletal myopathy, prepubertal growth delay, and distinctive facial gestalt. [2] Jul 30, 2019 — Diagnosis · Heart findings like dilated cardiomyopathy, hypertrophic cardiomyopathy and noncompaction of left ventricle [3] by J Finsterer · 2019 · Cited by 36 — Differential diagnoses that have to be excluded before diagnosing Barth syndrome include disorders in which 3-MGA is also increased, such as ... [4] Differential diagnosis includes hereditary, dilated and nutritional cardiomyopathy and idiopathic/cyclic neutropenia (see these terms). Antenatal diagnosis. [5] by SLN Clarke · 2013 · Cited by 387 — Key areas of differential diagnosis include metabolic and viral cardiomyopathies, mitochondrial diseases, and many causes of neutropenia and ... [6] Differential diagnosis. edit. Based on symptoms at time of presentation, the differential diagnosis may include other hereditary and/or nutritional causes of ... [7] by J Finsterer · 2019 · Cited by 36 — Differential diagnoses that have to be excluded before diagnosing Barth syndrome include disorders in which 3-MGA is also increased, such as ... [8] Apr 23, 2024 — Barth syndrome is a genetic disorder typically diagnosed in males at birth. It leads to cardiomyopathy (a weakened heart), neutropenia, and ... [9] Diagnosis of Barth syndrome is best achieved via cardiolipin ratio testing or, if ... Differential diagnosis. The metabolic differential for a dilated ...