Pediatr Cardiol. 2005 Oct 18
Effects of Acetyl-L-carnitine on Cardiac Dysautonomia in Rett Syndrome: Prevention of Sudden Death?
Guideri F, Acampa M, Hayek Y, Zappella M.
Department of Internal Medicine and Immunological Sciences, Section of Clinical Immunology, University of Siena, Viale Bracci, Siena, 53100, Italy, guideri@unisi.it.Abstract
There is a higher incidence of sudden death in patients with Rett syndrome than individuals in the general population. Previous studies have implicated cardiac dysautonomia and a long QT interval as causative factors. Because carnitine plays a critical role in cellular metabolism and may have beneficial effects on cardiac and nerve function, we investigated the effects of long-term treatment with acetyl-L-carnitine on heart rate variability and electrocardiographic abnormalities in 10 girls with Rett syndrome and compared the results with 12 control patients (girls with Rett syndrome who were not treated). The age range of the subjects was 2-21 years. The study design called for the evaluation of heart rate variability, corrected QT interval, and QTc dispersion. In the 10 Rett girls treated with acetyl-L-carnitine, a significant increase in heart rate variability was observed. To explain these results, we hypothesize that acetyl-L-carnitine has a neurotrophic action on the cardiac autonomic nervous system. This effect may reduce the risk of sudden death in patients with this syndrome.Lay Summary
The incidence of sudden death is greater in RTT than that of the non-RTT population - 0.3% per year versus 0.0013% per year, respectively. As we know, there is clinical and experimental evidence to show that the autonomic (or "involuntary") nervous system is altered to varying degrees in RTT. It is possible that this increased risk of sudden death is partial due to the occurrence of alterations in autonomic cardiac function. Interestingly, acetyl-L-carnitine (ALC) - a compound that affects autonomic cardiac activity - has been shown via experimental long-term treatment to have therapeutic advantages in normalizing autonomic cardiac activity in other disease states. In this study, the authors describe the effects of ALC treatment on a small group of RTT patients. They show that autonomic cardiac activity is better regulated in those RTT patients treated with ALC, than those RTT patients without ALC treatment. Although no major side effects or negative cardiac effects have been detected with this substance, large trials designed to examine the mortality rate or occurrence of deleterious effects are still needed to prove that ALC can protect RTT patients from sudden death. That said, the current observations provide encouraging evidence that cardiac dysfunction in RTT may be improved by ALC treatment.