Organic acid disorders and the ketogenic diet

Demeritte EL Ventimiglia J Coyne M Nigro MA. Detroit,
MI Child Neurology Society Abstract, 1996,

In a 17-month period we placed 91 patients on the ketogenic diet (KGD). The 61 patients who remained on the KGD were evaluated in an effort to identify metabolic effects, beyond the acute starvation period, that could contribute to the efficacy and complications of the diet and also to determine changes, if any, that might require intervention or discontinuation of the diet despite clinical success. We compared metabolic studies performed before and at least 1 month after diet initiation. There were no changes in electrolytes, liver function, or complete blood count. Triglyceride and cholesterol levels increased, as described by others. Proteins remained normal and glucose was unchanged, in contrast to the hypoglycemia that is seen during the fasting period. The ratio of free to bound carnitine decreased significantly, compatible with increased beta oxidation, warranting carnitine supplementation. Organic acid screening performed on 25 patients revealed that the 3-hydroxybutyric acid and acetoacetate were elevated as expected. Twenty-eight percent of these patients showed products indicating beta oxidation defect; four of these exhibited suberyl glycine and organic aciduria consistent with medium-chain acyl coenzyme A dehydrogenase deficiency and were taken off the diet. One severely impaired child died during ahyperpyrexic episode. Five patients were removed from the program for various other reasons. The KGD may reveal underlying fatty acid oxidative defects more readily and/or may, in part, be a measure of its anticonvulsant mechanism of action. We believe that organic acid screening should be done prior to and after initiation of the diet and carnitine supplements should be given routinely.

Hypocarnitinemia and the ketogenic diet

Rutledge SL Kinsman SL Geraghry MT Vining EPG Thomas G (Johns Hopkins)
Ann Neurol 1989;26;3;472

The primary function of L-carnitine is the transfer of long-chain fatty acids across the mitochondrial membrane. Secondary carnitine deficiencies of L-carnitine have been described in multiple clinical conditions, including organic acidemias, chronic hemodialysis, failure to thrive, and in children on valproate therapy. The ketogenic diet, as used in our institution, uses high amounts of fat (60-80% of daily caloric intake) as anticonvulsant therapy. The dietary fats are primarily animal fats and very rich in long-chain fatty acids. We measured plasma carnitine levels in 4 children who were on the ketogenic diet for 2 to 36 months. All 4 children had low free carnitine levels, and 3 of the 4 had low total carnitine levels. The acylcarnitine levels were normal or high, which increased the percentage of acyl to total carnitine to greater than 50% (normal 20-40%). There were no symptoms of carnitine deficiency. None of the 4 were on valproate. Extensive metabolic evaluation in 2 showed no evidence of an inborn error of metabolism. The lowest plasma carnitine levels were seen in the 2 patients on the diet for the longest intervals (11 and 36 months). One child had excellent seizure control on the diet. Three children had improved seizure control on the diet when adequate ketogenesis was attained, but there was difficult in maintaining high urinary ketone levels.

We do not know if the carnitine deficiency is secondary to 1) its increased utilisation during a diet rich in long-chain fatty acids, 2) decreased dietary intake on a diet moderately low in protein, or 3) excessive urinary loss of acylcarnitine esters. Perhaps it is due to a combination of these factors. It is interesting to speculate that this deficiency may make adequate ketogenesis more difficult to attain and if ketogenesis is a measure of effectiveness of the diet, may affect dietary efficacy in seizure control. We plan a larger, prospective study to evaluate carnitine status and the ketogenic diet and the effects of carnitine replacement therapy on dietary efficacy.

Carnitine deficiency in patients starting the ketogenic diet

Chez MG Buchanon C Kessler J Demski P Wagner E. Lake Forest, IL
1997 AAN Scientific Program Abstract

OBJECTIVE: Patients entering the Ketogenic diet often have failed multiple anticonvulsants and may be at risk for carnitine deficiency, placing additional stress on their metabolism of fatty acids. We looked at baseline carnitine levels prospectively in 12 patients starting the Ketogenic diet.

BACKGROUND: Clinical observation of patients initiating the ketogenic diet were suspected of carnitine deficiency based on severe symptomatic hypoglycemia during fasting and were found to have low total carnitine and elevated carnitine esters. Risk of carnitine deficiency may occur in chronic epilepsy patients who undertake the ketogenic diet.

DESIGN/METHODS: Twelve patients entering the Lake Forest Ketogenic Diet Program were informed that carnitine levels would be drawn as part of their baseline laboratory
studies, The 12 patients (age 6-24 years , ave.14.4 years, 7 female, 5 male) who had failed an average of 4.5 medications were assessed prospectively.

RESULTS: Total carnitine levels were deficient in 9/12 patients (range 10-28nmol/ml, average 21.5nmol/ml:[nl 31-61nmol/ml]). Acyl carnitine levels were elevated in 6/12 patients (range 13-54nmol/ml,average 29nmol/ml[nl2-13nmol/ml]). Both parameters were abnormal in 7 patients. Symptomatic Hypoglycemia (average serum glucose 28 mg/dl) occurred in 7/9 patients with low total carnitine and 5/6 paints with elevated acyl carnitine esters. Two patients with normal levels of carnitine and acyl carnitine esters were asymptomatic.

CONCLUSIONS: Patients with severe hypoglycemia initiating a ketogenic diet may have a carnitine deficiency. These patients are at risk due to chronic medication and seizures. We recommend routine screening of all patients who initiate the ketogenic diet.

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