The Minacious Dance of TANGO2 Deficiency in Brazilian Patients

TANGO2 deficiency disorder is an autosomal recessive disease characterised by neurodevelopmental delay, speech difficulties, intermittent ataxia, seizures, hypothyroidism, and metabolic with/without cardiac crises. Acute metabolic crises, frequently precipitated by infections or prolonged fasting, are associated with muscle weakness, rhabdomyolysis, hypoglycaemia, ataxia and prolonged QTc interval. Some patients can develop ventricular arrhythmias, cardiomyopathy, and cardiac arrest. Six patients from five families participated in this study, with a median age of 4.3 years. The symptoms included neurodevelopmental delay (83%), ataxia (66.6%), speech difficulties (83%), weakness (66.6%), head/body tilt (66.6%), exotropia (33.3%) and seizures (33.3%). Five patients had metabolic crises with elevated creatine phosphokinase serum (range: 7,000 to 260,000 U/L). One patient had a severe cardiac crisis and an implantable cardioverter-desfibrillator (ICD) was indicated. Their molecular investigation identified only two different alleles (c.605+1GA and exon 3-9 deletion) and only one family reported consanguinity. All patients have been taking multivitamin supplementation (with B5) for less than one year. The prevalence of patients with TANGO2 deficiency disorder in Brazil may be underestimated as genetic testing is not fully available and many of the symptoms are nonspecific with some lethal cases. Early diagnosis and appropriate family counselling are fundamental for crisis prevention, as well as a medical team specialised in metabolic and “electrical storm cardiac crises” for better outcomes.

Keywords: TANGO2, inborn errors of metabolism, metabolic disorder, cardiac crises