Arrythmias in inborn errors of metabolism

This is the ECG of a 6 year old boy who gave a history of repeated episodes of unexplained hypoglycaemic seizures in the first year of life. His tandem mass spectroscopy suggested a fatty acid oxidation defect. He was advised regular meals, avoidance of fasting, carnitine and biotin supplements and  oral oxcarbamazepine and clobazam on which he became seizure free.

He now came with a short history of fever and on routine examination was noted to have some missed beats. ECG showed bigeminy.

The questions I wanted to answer were 

1. Which are the inborn errors which present with arrhythmias?

2. How can we treat or prevent these?

The common causes of inborn errors of metabolism developing arrhythmias are fatty acid oxidation defects (FAOD), carnitine deficiency and mitochondrial disorders. Arrhythmias also occur in organic acidemias and later stages of storage disorders which affect the heart like Pompes, glycogen storage disorders, Gauchers and mucopolysaccharidosis.

 A beautiful paper in Circulation published in 1999 analysed 107 cases of fatty acid oxidation defects of whom 24 had arrhythmias. While ventricular arrhythmias were present in all types of FAOD's, conduction blocks and atrial arrhythmias were seen only in CPT II and carnitine acyl carnitine translocase. The carnitine transporter, CPT I and MCADs were not associated with arrhythmias. It appears one prime cause of arrhythmias is the accumulation of long chain acyl carnitines which have toxic effects on the phospholipids of the sarcolemma and disrupt various ion channels there. 

Avoidance of fasting and carnitine supplements may have some role in reducing arrhythmias but are not always successful.

A new paper basic science paper published in the International Journal of Molecular Science in April 2020, suggests that resveratrol ( found in grapes and red wine) and  etomoxir ( CPT1 inhibitor) may potentially have a role in preventing arrhythmias in VLCFAOD http://dx.doi.org/10.3390/ijms21072589.

Resveratrol works in (in vitro) in mild phenotypes who have some residual activity of VLCAD by reducing accumulation of very long chain acyl carnitines. Etomoxir works by inhibiting the production of long chain acyl carnitines. Both these drugs have been used to reduce post myocardial infarction related arrhythmias.