Intrafamilial Variability in 2 Siblings With TANGO2-Related Disorder

Area of Science:

• Genetics
• Neurology
• Metabolic disorders

Background:

• TANGO2-related disorder (TDD) is a rare autosomal recessive condition.
• It is characterized by episodic metabolic crises, rhabdomyolysis, encephalopathy, and cardiac arrhythmias.
• Phenotypic variability often leads to diagnostic delays.

Purpose of the Study:

• To report on two sisters with TDD exhibiting divergent clinical presentations.
• To highlight intrafamilial variability in TDD.
• To emphasize the importance of early recognition of TDD red flags.

Main Methods:

• Case report of two sisters with TDD.
• Genetic analysis identifying homozygous recurrent TANGO2 variant c.460G>A (p.Gly154Arg).
• Clinical evaluation including neurological and endocrine assessments.

Main Results:

• The sisters presented with different symptoms: developmental delay, hypoglycemia, and weakness versus hypotonia, ataxia, and behavioral issues.
• Routine metabolic testing was largely unremarkable between crises.
• Brain MRI studies were normal in both patients.

Conclusions:

• These cases demonstrate significant intrafamilial variability in TANGO2-related disorder.
• Early identification of neurologic and endocrine features is critical.
• Prompt molecular diagnosis is essential for effective management and improved outcomes.