TANGO2-Related Metabolic Encephalopathy and Arrhythmias

Alternate names

Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration; TANGO2; Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome; TANGO2 related disease

Definition

TANGO2-related metabolic encephalopathy and arrhythmias is a disease that can cause episodes of metabolic crises and abnormal heart rhythms (arrhythmia).

Summary

• A metabolic crisis is caused by having low blood sugar (hypoglycemia) and the buildup of toxic products in the blood.
• A metabolic crisis can occur in any person with a metabolic disorder, and they are more likely to occur after a person has gone long periods without eating or during an illness.

Epidemiology

The disease is most common in people who are of Caucasian or Hispanic/Latino descent.

Cause

TANGO2-related metabolic encephalopathy and arrhythmias is caused by a genetic change (mutation or pathogenic variant) in the TANGO2 gene.

Inheritance

Autosomal recessive inheritance, a 25% chance

The disease is inherited in an autosomal recessive manner.

Onset

Signs and symptoms of the disease are most likely to first occur during infancy or early childhood.

Signs and symptoms

• Most people with TANGO2-related metabolic encephalopathy and arrhythmias present with symptoms of a breakdown of muscle tissue (rhabdomyolysis).
• This can cause kidney damage and symptoms include fatigue, muscle weakness, and having a dark color of the urine.
• Other symptoms of TANGO2-related metabolic encephalopathy and arrhythmias include developmental delay, intellectual disability, seizures, hearing loss, low thyroid function (hypothyroidism) and trouble coordinating movements (ataxia).

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Elevated serum creatine kinase(Elevated blood creatine phosphokinase)
• EMG: myopathic abnormalities
• Increased serum lactate
• Intellectual disability(Mental deficiency)
• Ketonuria

30%-79% of people have these symptoms

• Abnormality of extrapyramidal motor function
• Acute rhabdomyolysis
• Arrhythmia(Abnormal heart rate)
• Ataxia
• Compensated hypothyroidism
• Delayed ability to walk
• Delayed speech and language development(Deficiency of speech development)
• Developmental regression(Loss of developmental milestones)
• Elevated hepatic transaminase(High liver enzymes)
• Feeding difficulties in infancy
• Gastrointestinal dysmotility
• Global brain atrophy(Generalized brain degeneration)
• Hyperammonemia(High blood ammonia levels)
• Incoordination(Difficulties in coordination)
• Lactic acidosis(Increased lactate in body)
• Moderate global developmental delay
• Prolonged QT interval

5%-29% of people have these symptoms

• Amblyopia(Lazy eye)
• Babinski sign
• Bilateral tonic-clonic seizure(Grand mal seizures)
• Cerebral visual impairment
• Clonus
• Dysphagia(Poor swallowing)
• Dystonia
• Elevated plasma acylcarnitine levels
• Focal impaired awareness seizure
• Generalized myoclonic seizure
• Generalized tonic seizure
• Hypertonia
• Hypertrophic cardiomyopathy(Enlarged and thickened heart muscle)
• Hypoglycemic seizures
• Infantile spasms
• Microcephaly(Abnormally small skull)
• Mild global developmental delay
• Multifocal seizures
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Optic atrophy
• Premature pubarche(Premature pubic hair growth)
• Premature thelarche(Premature breast development)
• Sensorineural hearing impairment
• Severe global developmental delay
• Spastic diplegia
• Spastic tetraplegia
• Stroke
• Supranuclear gaze palsy

1%-4% of people have these symptoms

• Global developmental delay
• Hypoglycemia(Low blood sugar)
• Prolonged QTc interval
• Seizure
• Torsade de pointes
• Ventricular tachycardia

Diagnosis

• The disease may be suspected in people who have a metabolic crisis, episodes of rhabdomyolysis, and arrhythmias.
• The diagnosis can be confirmed with genetic testing.

Treatment

Acute presentation:

• Early management during episodes of metabolic crises with aggressive intravenous hydration and urine alkalinization.
• Cardiac monitoring should include an early electrocardiogram (ECG), continuous ECG monitoring, and an echocardiogram to determine cardiac function. Arrhythmia management by an electrophysiologist is preferred
• Monitor electrolytes and treat as necessary to maintain normal levels of potassium, magnesium, and glucose
• Levothyroxine for hypothyroidism and steroid treatment for adrenal insufficiency, if determined. .

Non-acute presentation: Standard treatment of developmental delay/intellectual disability levothyroxine is the treatment of choice for hypothyroidism. Antiepileptics have been used for management of seizures.<ref>Lalani SR, Graham B, Burrage L, et al. TANGO2-Related Metabolic Encephalopathy and Arrhythmias. 2018 Jan 25 [Updated 2018 Dec 20]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK476443/</ref>[1].

References

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NIH genetic and rare disease info

• NIH info on TANGO2-Related Metabolic Encephalopathy and Arrhythmias

TANGO2-Related Metabolic Encephalopathy and Arrhythmias is a rare disease.

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