OUTCOME OF PYRUVATE-DEHYDROGENASE DEFICIENCY TREATED WITH KETOGENIC DIETS - STUDIES IN PATIENTS WITH IDENTICAL MUTATIONS

Inborn errors of the pyruvate dehydrogenase complex (PDC) are associat ed with lactic acidosis, neuroanatomic defects, developmental delay, a nd early death. PDC deficiency is a clinically heterogeneous disorder, with most mutations located in the coding region of the X-linked a su bunit of the first catalytic component, pyruvate dehydrogenase (E-1). Treatment of E-1 deficiency has included cofactor replacement, activat ion of PDC with dichloroacetate, and ketogenic diets. In this report, we describe the outcome of ketogenic diet treatment in seven boys with E-1 deficiency. These patients were divided into two groups based on their mutations (R349H, three patients; and R234G, four patients, two sibling pairs). All seven patients received ketogenic diets with varyi ng degrees of carbohydrate restriction. Clinical outcome was compared within each group and between siblings as related to the intensity and duration of dietary intervention. Subjects who either had the diet in itiated earlier in life or who were placed on greater carbohydrate res triction had increased longevity and improved mental development. Base d on the improved outcomes of patients with identical mutations, it ap pears that a nearly carbohydrate-free diet initiated shortly after bir th may be useful in the treatment of E-1 deficiency.