TANGO-2: A Rare Genetic Condition With Severe Clinical Presentation of Encephalopathy, Rhabdomyolysis, and Cardiac Rhythm Disorders in 2 Children.

Biallelic pathogenic or likely pathogenic variants in Transport and Golgi Organization 2 (TANGO-2) are associated with a spectrum of clinical features including encephalopathy, rhabdomyolysis, cardiac rhythm disorders, and neurologic regression. We are reporting on 2 unrelated children with biallelic TANGO-2 pathogenic variants. These variants were identified through a Next Generation Sequencing (NGS) panel of genes associated with hereditary rhabdomyolysis. Both children had a history of developmental delay, especially in their motor milestones. They also experienced episodic transient weakness with acute illness. One of the children's siblings had similar complaints and died at an early age. During their illness, both children developed extreme lethargy with very high CPK levels, lactic acidosis, rising trends of transaminases, and recurrent hypoglycemia. Both patients developed ventricular tachyarrhythmias, and the echocardiogram showed cardiomyopathy. Despite intensive symptomatic management, both patients died of cardiac failure because of fatal ventricular arrhythmia. Genetic testing revealed the presence of biallelic pathogenic variants TANGO-2. This rare genetic condition should be suspected in any patient with episodic recurrent weakness, rhabdomyolysis, abdominal pain, and cardiac arrhythmias, because of its diverse clinical presentation. However, early diagnosis is challenging because there are no specific biochemical markers for the disease. There is strong evidence that vitamin B supplementation can significantly reduce the number of metabolic crises in these children. Although this is not a targeted therapy, it can be a potentially life-saving treatment for these patients.