Tango 2 disease is a rare, inherited genetic condition first identified in recent years. The name is an acronym for “Transport and Golgi organization 2 homolog,” which refers to the specific gene involved. It is characterized by distinct episodes of severe illness as well as ongoing developmental issues. The condition is highly variable and can present differently from one person to another.
Symptoms and Clinical Presentation
A defining feature of Tango 2 disease is the occurrence of sudden, severe episodes known as metabolic crises. These events are set off by common triggers such as an infection, fever, or not eating for an extended period. During a crisis, an individual can experience a rapid breakdown of muscle tissue, known as rhabdomyolysis. This process releases a protein called myoglobin into the blood, which can lead to dark-colored urine and potentially cause kidney damage.
The metabolic crises are also marked by life-threatening heart rhythm problems, or arrhythmias. Individuals may experience recurrent ventricular tachycardia, a type of fast, abnormal heart rate which is dangerous if not treated promptly. Another symptom during these episodes is hypoglycemia, or low blood sugar, which can contribute to brain dysfunction known as encephalopathy. These crises are considered medical emergencies that require immediate intervention.
Outside of these acute crises, individuals with Tango 2 disease exhibit a range of baseline neurological symptoms. Many experience developmental delays in milestones like walking and talking. Intellectual disability of varying degrees is also common.
Other persistent neurological signs include hypotonia, which is low muscle tone that can make an individual seem “floppy,” and ataxia, problems with coordination and balance resulting in an unsteady gait. Some individuals also have seizures that occur separately from the metabolic crises. Additional symptoms include overactive reflexes, intermittent head tilting, and motor speech disorders.
The Genetic Basis of the Disorder
Tango 2 disease is caused by mutations in the TANGO2 gene. This gene provides instructions for making a protein that is thought to be involved in the transport and organization of other proteins between cellular structures, specifically the endoplasmic reticulum and the Golgi apparatus. When mutations occur in the TANGO2 gene, the resulting protein may be dysfunctional or absent, disrupting these cellular processes.
The inheritance pattern for this condition is autosomal recessive. This means an affected child must inherit two mutated copies of the TANGO2 gene—one from each parent. A person who has only one copy of the mutated gene is known as a carrier.
Carriers do not typically show any signs or symptoms of the disease because their one functional copy of the gene is sufficient to produce enough of the TANGO2 protein. It is estimated that approximately 1 in 566 people is a carrier of a defective TANGO2 gene. The condition only manifests when two carriers have a child who inherits the mutated gene from both of them.
Diagnosis Process
Diagnosis often begins with the recognition of its characteristic clinical signs, especially the sudden onset of a metabolic crisis. A physician may suspect the disorder in a child who presents with a combination of rhabdomyolysis, cardiac arrhythmias, and encephalopathy, particularly if the episode was triggered by an illness. The presence of underlying developmental delays or an unusual gait can also point a clinician toward considering this rare condition.
While clinical symptoms raise suspicion, the definitive diagnosis is achieved through molecular genetic testing. This type of testing analyzes an individual’s DNA to identify disease-causing mutations in both copies of the TANGO2 gene. Genetic testing is typically performed at specialized laboratories.
During an acute metabolic crisis, other diagnostic tests are used to manage the immediate situation. Blood tests are administered to measure levels of creatine kinase (CK), an enzyme that, when highly elevated, indicates significant muscle damage from rhabdomyolysis. Blood sugar levels are checked to detect hypoglycemia, and an electrocardiogram (ECG) is used to monitor the heart’s electrical activity and identify arrhythmias. Brain imaging, such as an MRI, might also be performed.
Management and Treatment Strategies
Currently, there is no cure for Tango 2 disease, so a primary strategy is managing symptoms and preventing crises by strictly avoiding known triggers. This includes preventing prolonged periods of fasting and aggressively treating any illnesses or fevers to reduce the risk of a crisis. Families often work with their medical team to establish a detailed emergency protocol to follow if a crisis begins.
During a metabolic crisis, treatment addresses the life-threatening symptoms. This requires hospitalization to monitor heart rhythm, electrolyte levels, and kidney function. Medications may be used to control dangerous arrhythmias, and in some cases, an implantable cardioverter-defibrillator (ICD) may be recommended to prevent future cardiac events. Intravenous fluids are administered to protect the kidneys from damage caused by rhabdomyolysis.
Long-term management involves a multidisciplinary team to address the ongoing neurological and developmental aspects of the disorder. Children benefit from a combination of physical, occupational, and speech therapies to help with muscle tone, coordination, and communication. Anti-seizure medications may be prescribed for those who experience epilepsy, and some individuals may require hormone replacement therapy for hypothyroidism, which can be an associated condition.