TANGO2 (transport and Golgi organization 2 homolog)
- was first identified in 2016 and encodes a protein that is postulated to be involved in redistributing the Golgi membranes into the endoplasmic reticulum (ER) (1,2)
- function of the TANGO2 gene is still not clear (2)
- data suggest multiple potential functions of the TANGO2 protein, including a role in fusion of the Golgi apparatus with the endoplasmic reticulum, and mitochondrial structure and function
- TANGO2 deficiency is hypothesised to induce dysfunction in lipid biosynthesis that is exacerbated under conditions that stress the body
- is a rare, genetic, metabolic disorder characterized by (2):
- developmental delay
- gait incoordination
- hypothyroidism
- recurrent crises with associated metabolic derangements, myositis, rhabdomyolysis, and severe cardiac tachyarrhythmias
Presentation is often with a metabolic crisis precipitated by an infection or other catabolic state (1,2):
- patients with TANGO2 deficiency generally have a history or current symptoms of psychomotor impairment characterized by ambulatory dysfunction and hypotonia as well as signs of neurodevelopmental decline
- features of metabolic crises may compose of findings of rhabdomyolysis, seizures, ECG abnormalities including prolonged QT intervals and/or type I Brugada pattern, and severe arrhythmias including potentially life-threatening recalcitrant ventricular tachycardia
- the diagnosis of TANGO2 deficiency should be considered in patients presenting in an acute metabolic crisis with life-threatening recalcitrant ventricular arrhythmias (2)
Reference:
- Dines J et al. TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants. Genet Med. 2019 Mar;21(3):601-607.
- Walters B, McConkey N, Imundo JR. TANGO2: A Rare but Important Mutation. J Innov Card Rhythm Manag. 2024 May 15;15(5):5871-5875.