Symptom Prevalence and Genotype-Phenotype Correlations in Patients With TANGO2-Related Metabolic Encephalopathy and...

TANGO2-related metabolic encephalopathy and arrhythmias (TRMEA) is a rare, phenotypically heterogeneous, neurological disease affecting children.

We conducted a chart review of five children with molecularly confirmed TRMEA diagnosed at our institution and compiled pathogenic variant frequency and symptom prevalence from cases previously reported in the literature.

Including those patients in our case series, 76 patients with TRMEA have been described. Developmental delay (93%) and/or regression (71%), spasticity (78%), and seizures (57%) are common in TRMEA and frequently precede life-threatening symptoms such as metabolic decompensation with lactic acidosis (83%), cardiomyopathy (38%), and cardiac arrhythmias (68%). Deletion of exons 3 to 9 is the most common pathogenic variant (39% of alleles). The majority of reported intragenic variants (17 of 27) result in disruption of the reading frame, and no clear genotype-phenotype correlations could be identified for those variants wherein the reading frame is maintained, highlighting instead the variable expressivity of the disease.

Patients with TRMEA frequently experience life-threatening complications that are preceded by common neurological symptoms underscoring the need for pediatric neurologists to be familiar with this condition. Additional work pertaining to disease pathophysiology and potential therapeutics is needed.