Abstracts

Rationale: Carnitine deficiency has been documented in children treated with the classic ketogenic diet (KD), but not the medium chain triglyceride KD (MCTKD). Intake of carnitine is low on both KDs and the demand for carnitine is increased due to the high fat intake. Symptoms of carnitine deficiency can be chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction. As carnitine is required for the transport of long-chain fatty acids into the mitrochondria for -oxidation, but not medium-chain fatty acids (MCFA), the MCTKD should present less of a risk for carnitine deficiency then the classic KD. The objective of this study is to compare the incidence of carnitine deficiency in children treated with the MCT and classic KDs.Methods: A retrospective review was performed of serum total and free carnitine in children treated with a KD for intractable epilepsy from 1/2005 to 5/2013. Forty-two children were treated with the classic KD (mean age SD=4.8 years 3.2) and 27 with the MCTKD (mean age SD=6.1 years 2.4). Carnitine levels were measured prior to diet initiation and at 3, 6, 12, 18, 24, 30 and 36 months follow-up. Children with documented carnitine deficiency were treated with L-carnitine at a dosage of 50-100 mg/Kg body weight to return carnitine levels to the normal range.Results: Prior to initiation of the classic KD, 13 children (31%) had low free carnitine and 2 (5%) had low total carnitine. During treatment with the classic KD, 27 (64%) children had at least 1 low free carnitine (mean SD=20.02 3.90umol/L) (normal range:26.0-60.0 umol/L) and 9 (21%) had at least 1 low total carnitine (mean SD=24.09 3.79 umol/L) (normal range: 32.0-84.0 umol/L). Prior to initiation of the MCTKD, 4 (15%) children had low free carnitine and 1 (3.7%) had low total carnitine. During the MCTKD treatment, 20 (74%) children had at least 1 low free carnitine (mean SD=19.79 4.77 umol/L) and 9 (33%) had low total carnitine (mean SD=26.47 4.45 umol/L). There is no significant difference in free carnitine (p= 0.787) and total carnitine (p=0.1785) levels in those children treated with the classic and MCT KDs. Also, there is no significant difference in duration of diet therapy prior to the development of the first low serum free carnitine (p=0.59) on the classic KD (mean SD=11.0 0.6 months) and the MCTKD (mean SD= 9.1 9.2).Conclusions: MCFA do not require carnitine to enter the mitochondria. However, carnitine does play an important role in MCTKD by removing acyl and acetyl groups from mitochondria and in restoring the intramitochondrial CoA level. Fat substrates are converted into compounds that may be utilized by tissues that do not normally oxidize fatty acids, creating an interorgan energy cycle. With up to 70% MCT contributing to the daily calorie intake in MCTKD, children may be at risk for carnitine deficiency. We have demonstrated that all children treated with KDs are at risk for carnitine deficiency, regardless of diet subtype. Carnitine status should be routinely monitored and L-carnitine supplement should be implemented, as needed.