TANGO2-related disease. TANGO2-Related Metabolic Encephalopathy and Arrhythmias. Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration.
Incidence
TANGO2-related metabolic encephalopathy and arrhythmias is a rare disorder. Less than 30 cases have been reported.
Clinical Characteristics
TANGO2-related metabolic encephalopathy and arrhythmias is a rare genetic disorder caused by variants in the TANGO2 gene. The condition can result in episodes of acute metabolic crises triggered by infection, fasting, stress or dehydration resulting in arrhythmias, rhabdomyolysis and other complications. During an acute metabolic crisis, there may be hypoglycemia, elevated liver enzymes, elevated creatinine kinase and troponin, hyperammonemia and hyperlactacidemia, profound muscle weakness, ataxia and disorientation which can lead to a comatose state. During acute illness, transient electrocardiogram changes can be seen; the most common being QT prolongation. Life-threatening recurrent ventricular tachycardia or torsade de pointes occurs primarily during times of acute illness. Creatine phosphokinase (CPK) can be significantly elevated in some individuals (>200,000 U/l). The first episode of myoglobinuria has been known to occur as early as age five months which can lead to kidney failure.
Additional signs and symptoms include mild to severe intellectual disability in most patients, developmental delay, regression, ataxia, hypothyroidism in one third of patients and seizures in more than 75% of individuals. In rare instances, affected children have developed sensorineural hearing loss. Adrenal insufficiency may also occur.
Prominent lateral ventricles, with progressive brain atrophy on MRI examination, have been reported in several affected individuals. While some older individuals have normal brain imaging studies, generalized cerebral atrophy has been described in young infants with early disease presentation.
Spasticity of lower extremities, hyperreflexia, and clonus have been reported. Dysarthria, myopathic facies, intermittent head tilt, and drooling can be observed in individuals between acute metabolic crises.
A variety of seizure types have been reported, including generalized myoclonic and atonic seizures. Seizures are generally responsive to anti-seizure medications in individuals with TANGO2-related metabolic encephalopathy and arrhythmias, although refractory epilepsy has been reported.
Intermittent exotropia has been observed in affected individuals. Rare individuals have been diagnosed with optic atrophy.
Precipitants
Acute metabolic crises can be triggered by infection, fasting, stress or dehydration.
Provocation Tests
None
Diagnostic Procedures
The diagnosis of TANGO2-related metabolic encephalopathy and arrhythmias is established in a proband by identification of biallelic pathogenic variants in TANGO2 on molecular genetic testing.