Challenges in managing metabolic crises and arrhythmias in TANGO2 mutation TANGO2 mutation is a rare genetic mutation characterized by metabolic crises associated with rhabdomyolysis, hypoglycemia, metabolic acidosis, encephalopathy, and life-threatening arrhythmias. There is a paucity of literature regarding the prevention or acute management of these metabolic crises and their sequelae

1. Section of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital
Challenges in managing metabolic crises and arrhythmias in TANGO2 mutation
INTRODUCTION CASE DESCRIPTION DISCUSSION AND IMPLICATIONS
TANGO2 mutation is a rare genetic mutation
characterized by metabolic crises associated
with rhabdomyolysis, hypoglycemia,
metabolic acidosis, encephalopathy, and life-
threatening arrhythmias. There is a paucity of
literature regarding the prevention or acute
management of these metabolic crises and
their sequelae
Fig 1: EKG on day of admission to CICU showing normal sinus
rhythm. Type 1 Brugada. ST depression in inferolateral leads.
Prolonged QTc (518msec), Nonspecific ST and T wave abnormality
•Challenge to medical team to manage his
arrhythmias with isoproterenol in the setting of
Brugada pattern on EKG
•Evidence of Brugada syndrome only presents
during metabolic crises, which also provokes
arrhythmias
•No clinical correlates associated with his
worsening metabolic crises to facilitate
projection of his trajectory of illness, which made
it difficult to manage him outpatient and at
outside facilities
•Due to presence of Brugada syndrome, lack of
treatment options if isoproterenol and
magnesium were inadequate
•Underlying condition made him ineligible for
ECMO and heart transplant
•Despite many metabolic crises, all of which were
associated with rhabdomyolysis, kidney function
has always remained normal
•Moral and ethical challenges due to
degenerative nature of disease and difficulty in
determining when care should be limited to
preserve quality of life
REFERENCES
1. Lalani, Seema R., et al. “Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic
Crises, and Cardiac Arrhythmia Due to Bi-Allelic TANGO2 Mutations.” The American
Journal of Human Genetics, vol. 98, no. 2, 2016, pp. 347–357.
Jill Zender, RN, CPNP-AC, Raysa Morales-Demori, MD, Marc Anders, MD
• Presented in 2014, at 2 years of age, with difficulty walking, progressive
neurologic decline, hypoglycemia, and an episode of unresponsiveness
• Whole Exome Sequencing obtained that demonstrated a homozygous
pathogenic variant of p.Gly154Arg in the TANGO2 gene in March 2016
• Presented in March 2018 with fatigue, hematuria, right lower back and
bilateral leg pain, hypoglycemia and Creatinine Kinase (CK) >64,000 u/L
without evidence of Acute Kidney Injury (AKI)
• On EKG had findings consistent with Brugada Syndrome, which was not
present on previous EKGs, and QTc >500 ms
• Throughout CICU admission, never developed AKI despite CK >64,000 u/L
for over a week
• Began to have multiple episodes of ventricular bigeminy and Torsades de
pointes (TdP), which were initially treated with Magnesium sulfate
(maintaining magnesium level >2.4 mg/dL) and esmolol infusion
• Transitioned to isoproterenol because ventricular bigeminy and TdP more
prevalent with heart rate <120 bpm
• Since initial CICU admission, has required readmission multiple times for
management of metabolic crises and arrhythmias
• Each presentation has been characterized by significantly elevated CK levels
without AKI, frequent arrhythmias and marked neurologic decline with
difficulty speaking and swallowing
• When metabolic crises resolve and CK levels normalize, his arrhythmia
burden ceases and he regains motor function
• It remains unclear what leads to the occurrence and resolution of each crises