title: Effect of optimal dietary therapy upon visual function in children with long-chain 3-hydroxyacyl CoA dehydrogenase and trifunctional protein deficiency.
abstract: The objective of this prospective cohort study was to determine if dietary therapy including docosahexaenoic acid (DHA; C22:6omega-3) supplementation prevents the progression of the severe chorioretinopathy that develops in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency. Physical, biochemical, and ophthalmological evaluations, including electroretinogram (ERG) and visual acuity by evoked potential (VEP), were performed at baseline and annually following the initiation of 65-130 mg/day DHA supplementation and continued treatment with a low-fat diet. Fourteen children with LCHAD or TFP deficiency, 1-12 years of age at enrollment, were followed for 2-5 years. Three subjects with TFP beta-subunit mutations had normal appearance of the posterior pole of the ocular fundi at enrollment and no changes over the course of the study. Eleven subjects who were homozygote and heterozygote for the common mutation, c.1528G>C, had no change to severe progression of atrophy of the choroid and retina with time. Of these, four subjects had marked to severe chorioretinopathy associated with high levels of plasma hydroxyacylcarnitines and decreased color, night and/or central vision during the study. The plasma level of long-chain 3-hydroxyacylcarnitines, metabolites that accumulate as a result of LCHAD and TFP deficiency, was found to be negatively correlated with maximum ERG amplitude (Rmax) (p=0.0038, R2=0.62). In addition, subjects with sustained low plasma long-chain 3-hydroxyacylcarnitines maintained higher ERG amplitudes with time compared to subjects with chronically high 3-hydroxyacylcarnitines. Visual acuity, as determined with the VEP, appeared to increase with time on DHA supplementation (p=0.051) and there was a trend for a positive correlation with plasma DHA concentrations (p=0.075, R2=0.31). Thus, optimal dietary therapy as indicated by low plasma 3-hydroxyacylcarnitine and high plasma DHA concentrations was associated with retention of retinal function and visual acuity in children with LCHAD or TFP deficiency.
authors.affiliation: Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA. gillingm@ohsu.edu
authors.forename: Melanie B
authors.initials: MB
authors.lastname: Gillingham
authors.forename: Richard G
authors.initials: RG
authors.lastname: Weleber
authors.forename: Martha
authors.initials: M
authors.lastname: Neuringer
authors.forename: William E
authors.initials: WE
authors.lastname: Connor
authors.forename: Monte
authors.initials: M
authors.lastname: Mills
authors.forename: Sandy
authors.initials: S
authors.lastname: van Calcar
authors.forename: James
authors.initials: J
authors.lastname: Ver Hoeve
authors.forename: Jon
authors.initials: J
authors.lastname: Wolff
authors.forename: Cary O
authors.initials: CO
authors.lastname: Harding
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency*; D015862:Choroid Diseases / Q000178:diet therapy / Q000503:physiopathology; D003677:Deficiency Diseases / Q000178:diet therapy* / Q000503:physiopathology*; D004596:Electroretinography; D005074:Evoked Potentials, Visual; D005227:Fatty Acids / Q000097:blood; D006801:Humans; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D012164:Retinal Diseases / Q000178:diet therapy / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D005227:Fatty Acids; D015094:3-Hydroxyacyl CoA Dehydrogenases; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase