TANGO2: A Rare but Important Mutation 2024 Walters et al

Abstract

We report the case of a 7-year-old boy who presented with post-viral myositis, rhabdomyolysis, and hepatitis, who was later readmitted due to a seizure-like activity and ultimately found to have episodes of recalcitrant polymorphic ventricular tachycardia secondary to simultaneous QT prolongation and severe hypothyroidism.

Temporary transvenous atrial pacing was successful at controlling the ventricular arrhythmias in the intensive care unit. With levothyroxine therapy and cessation of QT-prolonging medications, the corrected QT (QTc) normalized. A comprehensive arrhythmia panel identified a pathogenic mutation in KCNQ1, consistent with long QT syndrome (LQTS) type 1.

After the patient experienced progressive neurodegeneration and seizures, he was referred to a genetics clinic to rule out genetic epilepsy. On the epilepsy panel of genetic testing, he was found to have two pathogenic variants in TANGO2. TANGO2 deficiency explains the initial presentation of myositis, rhabdomyolysis, hypothyroidism, and life-threatening arrhythmias surrounding a viral illness more so than the initial diagnosis of mere LQTS. However, the TANGO2 gene is not included in most comprehensive arrhythmia and cardiomyopathy panels.

TANGO2 deficiency is a rare condition that often presents with arrhythmias but may be unfamiliar to many cardiologists and electrophysiologists. This case describes management strategies and caveats, which could aid in the successful diagnosis and treatment of TANGO2 deficiency at the time of presentation.

PubMed abstract only available at time of posting, https://pubmed.ncbi.nlm.nih.gov/38808169/

 

There's an interesting Reddit post of someone with ME/CFS who eventually found out they have this. After some dietary changes, they've been in remission for 14 months.

Link

 

I wonder how this would be hypothetically differentiated from ME/CFS without a genetic test.

 

Since ME/CFS is diagnosed based on symptoms, I don't think this makes sense. If they fit the criteria, then by definition they had it. There might be a thousand causes of ME/CFS, and this is just one.

 

So technically this could be 1/10’000th or whatever of what constitutes the ME/CFS syndrome construct.

But what I meant to ask in my comment is are there any symptomatic differences between this genetic disease and ME/CFS.

 

Interesting does this suggest that ME is a hodgepodge of different conditions?

Let’s hope things like this is something Decode ME might pick up on.

 

If your urine really is a dark brown (please google it for comparison) then that is essentially always an emergency. If it looks like Cola, you have to go to the hospital.

 

Oh yeah, there seem to be various presentations of the disease. Maybe some look like ME/CFS, some don't. From Wikipedia:

Diagnosis

Prognosis

 

Looks complicated. I wish it was standard medical practice to order WGS of severe people. Would make a fascinating dataset and be very interesting to see what proportion actually have known diseases like that.

I’m excited for SequenceME.

 

A heterozygous missense mutation in adolescent-onset very long-chain acyl-CoA dehydrogenase deficiency with exercise-induced rhabdomyolysis, 2015, Hisahara et al

Adult‐onset very‐long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD), 2020, Fatehi et al

Diagnostic assessment and long-term follow-up of 13 patients with Very Long-Chain Acyl-Coenzyme A dehydrogenase (VLCAD) deficiency, 2009, Laforêt et al

Timeline of PEM not quite the same in that last paper.

But the person on Reddit said their PEM started 24 hours post exertion.

 

Yep, and the symptoms look very different too.

Not really a picture of ME/CFS I'd recognise!