Remote monitoring in TANGO2 deficiency disorder and the protective role of B-complex vitamins

Introduction

TANGO2 deficiency disorder (TDD; OMIM: #616830) is a rare, life-threatening condition caused by biallelic pathogenic variants in the TANGO2 gene. TDD is characterised by recurrent metabolic crises and severe cardiac arrhythmias. During metabolic crises, life-threatening arrhythmias are frequently observed and often remain unresponsive to standard therapies when B-complex vitamin supplementation is not provided in advance. However, the cardiac rhythm behaviour exhibited during the intercrisis period remains to be fully elucidated. Continuous monitoring with implantable loop recorders (ILRs) offers a valuable approach to identifying potential subclinical cardiac manifestations in these patients.

Purpose

The objective of this study is to provide a detailed description of subclinical arrhythmic events detected during intercrisis in TDD patients by remote monitoring, and to evaluate the impact of vitamin B supplementation on arrhythmic outcomes.

Methodology: A cohort of 12 paediatric patients assessed during 2015-2025 with biallelic pathogenic variants in TANGO2 was observed both retrospectively and prospectively. Patients who received an ILR implant were monitored via a remote telemetry platform. A rigorous analysis was conducted on clinical data and arrhythmic events. Following a preliminary observation period, patients were administered B-complex supplementation, including B-50 complex (50 mg of: thiamine, riboflavin, niacin, pantothenic acid, inositol and choline bitartrate; 50 µg of vitamin B12 and biotin; 5 mg of pyridoxine; 400 µg of folic acid), 500 mg of pantothenic acid, and 5 mg of folic acid; once a day.

Results

Continuous intercrisis monitoring with ILRs identified subclinical rhythm abnormalities in six of the 12 TDD patients (50%) (median age 14.23 years, IQR=8.9 years). The occurrence of brady- and tachyarrhythmic events was detected during intercrisis monitoring. Tachyarrhythmic findings comprised prolonged QTc intervals in 5 patients (41.3%), supraventricular tachycardia (8.3%), and atrial flutter (8.3%), while bradyarrhythmias included sinus bradycardia in 2 patients (16.7%), pauses exceeding 3 seconds in 2 patients (16.7%), and Wenckebach atrioventricular block in 2 patients (16.7%). After the initiation of B-complex vitamin supplementation, all arrhythmic events were resolved, except for one case (8.3%) of bradyarrhythmia with recurrent pauses, which necessitated pacemaker implantation.

Conclusions

Continuous rhythm monitoring identified subclinical arrhythmias during the intercrisis period in TDD. B-complex vitamin supplementation effectively suppressed these abnormalities. Persistent bradyarrhythmias with pauses indicate a distinct conduction phenotype. These findings support the value of remote rhythm surveillance and the protective role of B-vitamins in TDD arrhythmias beyond acute crises.