TANGO2-related metabolic encephalopathy and arrythmias

What is TANGO2-related metabolic encephalopathy and arrhythmia?

TANGO2-related metabolic encephalopathy and arrhythmia, also known as TRMEA, is a rare and newly recognized disorder that affects children. It is characterized by a combination of metabolic crisis, lethal cardiac arrhythmias, and cardiomyopathy [5].

Symptoms and Complications

Individuals with TANGO2-related metabolic encephalopathy and arrhythmias can present in acute metabolic crisis, which may include hypoglycemia (low blood sugar), elevated lactate levels, and mild acidosis [6]. This condition can also lead to irregularities in the rhythm of the heart (arrhythmias) and breakdown of muscle tissue (rhabdomyolysis) during an episode [1].

Causes and Genetics

TANGO2 deficiency disorder (TDD) is an autosomal recessive disease associated with TRMEA. This means that a person must inherit two copies of the mutated TANGO2 gene, one from each parent, to develop this condition [5]. The genetic basis of TRMEA was first described in 2016 and has since been recognized as a distinct clinical entity.

References

• [1] Irregularities in the rhythm of the heart (arrhythmias), the breakdown of muscle tissue (rhabdomyolysis) and other complications can occur during an episode.
• [5] TANGO2 deficiency disorder (TDD) is an autosomal recessive disease associated with metabolic crisis, lethal cardiac arrhythmias, and cardiomyopathy.
• [6] Individuals with TANGO2-related metabolic encephalopathy and arrhythmias can present in acute metabolic crisis (hypoglycemia, elevated lactate, mild acidosis).
• [9] Background: TANGO2-related metabolic encephalopathy and arrhythmias (TRMEA) is a rare, phenotypically heterogeneous, neurological disease affecting children.

Symptoms of TANGO2-related Metabolic Encephalopathy and Arrhythmia

TANGO2-related metabolic encephalopathy and arrhythmia, also known as TANGO2 disease, is a rare disorder that can cause various symptoms. According to the search results, some of the common signs and symptoms of this condition include:

• Profound low blood sugars: This is one of the primary symptoms of TANGO2-related metabolic encephalopathy and arrhythmia (TRMEA) [3].
• Altered mental status: Individuals with TRMEA may present with altered mental status, which can range from mild confusion to coma-like states [3].
• Rhabdomyolysis: This is a breakdown of muscle tissue that can cause severe complications, including kidney damage and cardiac arrhythmias [5].
• Gait incoordination: Some people with TRMEA may experience gait incoordination, which can progress to unsteady gait or difficulty walking [6].
• Developmental delays: Children with TANGO2 disease may experience developmental delays, including cognitive, speech, and motor skill delays [7].
• Seizures: Seizures are a common feature of TRMEA, and they can range from mild to severe [8].
• Cardiac arrhythmias: Cardiac arrhythmias, or irregular heartbeats, are another symptom of TANGO2 disease [9].

These symptoms can vary in severity and may not be present in all individuals with TANGO2-related metabolic encephalopathy and arrhythmia. If you suspect that someone has this condition, it is essential to seek medical attention immediately.

References: [3] - Symptoms of Tango2 include profound low blood sugars and altered mental status, which was how Aislynn presented when brought to Cincinnati ... [5] - Most people with TANGO2-related metabolic encephalopathy and arrhythmias present with symptoms of a breakdown of muscle tissue (rhabdomyolysis). [6] - Individuals who do not present in metabolic crises may present with gait incoordination, progressively unsteady gait, difficulty with speech, or clumsiness. [7] - Symptoms include developmental, cognitive, and speech delays; episodic ataxia; hypothyroidism; and seizures. Metabolic stressors such as illness and prolonged ... [8] - Primary features include metabolic crisis with rhabdomyolysis, encephalopathy, intellectual disability, seizures, and cardiac arrhythmias. [9] - TANGO2-related metabolic encephalopathy and arrhythmias ... signs and symptoms. ... metabolic crisis with severe rhabdomyolysis and malignant cardiac arrhythmia.

Diagnostic Tests for TANGO2-related Metabolic Encephalopathy and Arrhythmias

The diagnosis of TANGO2-related metabolic encephalopathy and arrhythmia is established through a combination of clinical evaluation, specialized tests, and molecular genetic testing.

• Molecular Genetic Testing: The diagnosis of TANGO2 deficiency is established in a proband with biallelic pathogenic variants in TANGO2 identified by molecular genetic testing [8]. This test involves analyzing the genes to confirm the presence of mutations that cause the condition.
• Clinical Evaluation: A thorough clinical evaluation is necessary to identify individuals who may have TANGO2-related metabolic encephalopathy and arrhythmia. This includes assessing developmental milestones, neurological problems, and other signs and symptoms [4].
• Specialized Tests: Additional specialized tests may be required to confirm the diagnosis, such as:
  • Electrocardiogram (ECG) to assess heart rhythm and detect arrhythmias
  • Echocardiogram to evaluate heart function and structure
  • Blood tests to measure levels of certain enzymes and metabolites
  • Imaging studies (e.g., MRI or CT scans) to rule out other conditions that may cause similar symptoms

Key Points

• Molecular genetic testing is the gold standard for diagnosing TANGO2 deficiency.
• Clinical evaluation and specialized tests are necessary to confirm the diagnosis.
• A combination of these approaches can help establish a definitive diagnosis.

References:

[4] - The complete TANGO2-related phenotype often emerges over time. 3,6 The clinical presentation shows a similar neurological phenotype combined with severe recurrent metabolic crises resulting in rhabdomyolysis, severe encephalopathy, and life-threatening arrhythmias. 4,5,8 [8] - The diagnosis of TANGO2 deficiency is established in a proband with biallelic pathogenic variants in TANGO2 identified by molecular genetic testing. [3] - A thorough clinical evaluation and a variety of specialized tests are necessary to diagnose this condition.

Treatment Options for TANGO2-related Metabolic Encephalopathy and Arrhythmia

TANGO2-related metabolic encephalopathy and arrhythmia, also known as TANGO2 disease, is a rare disorder that requires prompt treatment to manage its symptoms. The management of this condition involves a multi-faceted approach, including medications and treatments to control the metabolic crisis and prevent arrhythmias.

Medications for Metabolic Crisis

A metabolic crisis is a medical emergency that requires immediate attention. According to search result [2], during acute metabolic crises, the management of arrhythmias relies on metabolic control. Therefore, beyond the tailored antiarrhythmic therapy, medications such as intravenous magnesium and isoproterenol may be used to manage the metabolic crisis.

Folate as a Potential Treatment

Recent studies have suggested that folate may be a potential treatment for lethal ventricular arrhythmias in TANGO2-deficiency disorder. Search result [4] reports that folate ameliorates arrhythmias in patient-derived TANGO2-deficient iPSC-CMs. This finding suggests that folate may be a useful adjunctive therapy in the management of TANGO2-related metabolic encephalopathy and arrhythmia.

Other Treatment Options

In addition to medications, other treatment options are available for individuals with TANGO2 deficiency. Search result [6] reports that heart transplantation has been considered as a treatment option for TANGO2-related cardiomyopathy. Furthermore, search result [8] suggests that targeted therapy, including daily supplementation with a multivitamin, may be beneficial in managing the symptoms of this condition.

Current Treatment Guidelines

While there is no cure for TANGO2 disease, current treatment guidelines recommend maintaining adequate blood glucose levels and preventing metabolic decompensations. Search result [7] reports that kids with TANGO2 disease should receive daily supplementation with a multivitamin to prevent metabolic decompensations.

Conclusion

In conclusion, the treatment of TANGO2-related metabolic encephalopathy and arrhythmia involves a multi-faceted approach, including medications and treatments to control the metabolic crisis and prevent arrhythmias. Folate has been suggested as a potential treatment for lethal ventricular arrhythmias in TANGO2-deficiency disorder, while other treatment options such as heart transplantation and targeted therapy may also be beneficial.

References

• [1] SA Gomes (2023) - TANGO2-related metabolic encephalopathy and arrhythmia
• [2] SA Gomes (2023) - Management of arrhythmias in acute metabolic crises
• [4] W Xu (2024) - Folate as a potential treatment for lethal ventricular arrhythmias in TANGO2-deficiency disorder
• [6] JK Meisner (2020) - Heart Transplantation for TANGO2-Related Metabolic Encephalopathy and Arrhythmia Syndrome–Associated Cardiomyopathy
• [8] FDA uses science and data to ensure that approved drugs are of a high quality, safe, and effective.

The differential diagnosis for TANGO2-related metabolic encephalopathy and arrhythmia involves considering various conditions that present with similar symptoms, such as developmental delay, seizures, ataxia, and acute metabolic crises. Some of the key conditions to consider in the differential diagnosis are:

• Mitochondrial disorders: These can cause a range of symptoms including developmental delay, seizures, and muscle weakness, which overlap with those seen in TANGO2-related metabolic encephalopathy and arrhythmia.
• Metabolic disorders: Conditions such as Pompe disease, McArdle disease, and Tarui disease can present with acute metabolic crises, hypoglycemia, and elevated lactate levels, similar to TANGO2-related metabolic encephalopathy and arrhythmia.
• Neurodegenerative disorders: Conditions like Rett syndrome, Angelman syndrome, and Prader-Willi syndrome can cause developmental delay, seizures, and ataxia, which may be confused with TANGO2-related metabolic encephalopathy and arrhythmia.
• Cardiac channelopathies: These conditions, such as long QT syndrome and Brugada syndrome, can cause cardiac arrhythmias and sudden death, similar to the life-limiting medical complications seen in TANGO2-related metabolic encephalopathy and arrhythmia.

It is essential to consider these differential diagnoses when evaluating patients with suspected TANGO2-related metabolic encephalopathy and arrhythmia. A comprehensive diagnostic workup, including genetic testing for TANGO2 mutations, electrocardiogram (ECG) analysis, and biochemical assessments, can help differentiate between these conditions and guide targeted therapeutic interventions.

References:

• [1] Individuals with TANGO2-related metabolic encephalopathy and arrhythmias can present in acute metabolic crisis (hypoglycemia, elevated lactate,