From Metabolic Crises to Epileptic Encephalopathy: TANGO2 Deficiency Disorder due to Homozygous Multi-exon Deletion.

Abstract

TANGO2 deficiency disorder is a rare, autosomal recessive, neurometabolic condition typically characterized by recurrent metabolic crises, rhabdomyolysis, cardiac arrhythmias, and neurodegeneration. We report a 5-year-old boy with normal early development followed by fever-triggered metabolic encephalopathy from 10 months, associated with severe high anion-gap metabolic acidosis. He subsequently developed epileptic spasms with hypsarrhythmia, evolving into refractory epilepsy and profound developmental impairment. Serial neuroimaging showed early cortical diffusion restriction followed by progressive cerebral atrophy. Notably, classical features such as rhabdomyolysis, cardiac involvement, and TANGO2 spells were absent, and metabolic evaluation was largely unremarkable between episodes. Genetic analysis identified a homozygous 3.6-kb deletion involving exons 4 to 6 of the TANGO2 gene. This case highlights that TANGO2 deficiency may present predominantly as a developmental and epileptic encephalopathy phenotype and is more commonly due to multi-exon deletions rather than single-nucleotide variations as seen in other inherited metabolic disorders. Early genetic testing, including copy number analysis, is essential for diagnosis and management.