title: Outcome of pyruvate dehydrogenase deficiency treated with ketogenic diets. Studies in patients with identical mutations.
abstract: Inborn errors of the pyruvate dehydrogenase complex (PDC) are associated with lactic acidosis, neuroanatomic defects, developmental delay, and early death. PDC deficiency is a clinically heterogeneous disorder, with most mutations located in the coding region of the X-linked alpha subunit of the first catalytic component, pyruvate dehydrogenase (E1). Treatment of E1 deficiency hs included cofactor replacement, activation of PDC with dichloroacetate, and ketogenic diets. In this report, we describe the outcome of ketogenic diet treatment in seven boys with E1 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 varying 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 initiated earlier in life or who were placed on greater carbohydrate restriction had increased longevity and improved mental development. Based on the improved outcomes of patients with identical mutations, it appears that a nearly carbohydrate-free diet initiated shortly after birth may be useful in the treatment of E1 deficiency.
authors.affiliation: Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-6004, USA.
authors.forename: I D
authors.initials: ID
authors.lastname: Wexler
authors.forename: S G
authors.initials: SG
authors.lastname: Hemalatha
authors.forename: J
authors.initials: J
authors.lastname: McConnell
authors.forename: N R
authors.initials: NR
authors.lastname: Buist
authors.forename: H H
authors.initials: HH
authors.lastname: Dahl
authors.forename: S A
authors.initials: SA
authors.lastname: Berry
authors.forename: S D
authors.initials: SD
authors.lastname: Cederbaum
authors.forename: M S
authors.initials: MS
authors.lastname: Patel
authors.forename: D S
authors.initials: DS
authors.lastname: Kerr
mesh_terms: D002657:Child Development; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D006801:Humans; D007231:Infant, Newborn; D007657:Ketone Bodies / Q000096:biosynthesis*; D008136:Longevity; D008297:Male; D009154:Mutation; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D004040:Dietary Carbohydrates; D007657:Ketone Bodies