[Please Note: No new subjects are being enrolled for this study. Because we do have experience with this, and one of the only 6 ophthalmologist board certified in both ophthalmology and genetics, we can evaluate subjects clinically if patients are interested.]

We followed 14 children with LCHAD or TFP deficiency for 2-5 years. Physical, biochemical and ophthalmological evaluations, including electroretinogram (ERG) and visual acuity by evoked potential (VEP), were performed at baseline and every year following the beginning of docosahexaenoic acid (DHA) supplementation and continued treatment with a low-fat diet. 65 mg DHA per day was provided for children under 50 pounds and 120 mg DHA per day was provided for children over 50 pounds in a concentrated gel cap that provided little other long-chain fat (Neuromins, Martek Biosciences Inc.).

Three children with TFP b -subunit mutations had normal appearance of retina at enrollment and no changes over the course of the study. The other eleven subjects were homogyzous or heterogyzous for the common LCHAD mutation, G1528C. They had no change to severe progression of pigmentary retinopathy with time. Four children 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 the electroretinogram. Children with sustained low plasma long-chain 3-hydroxyacylcarnitines maintained higher ERG amplitudes with time compared to subjects with chronically high 3-hydroxyacylcarnitines.

VEP appeared to increase with time on DHA supplementation and there was a trend for a positive correlation with plasma DHA concentrations. 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. Optimal dietary therapy was defined as maintaining low plasma hydroxyacylcarnitine levels (the sum of the long-chain hydroyxacylcarnitine species under 2 mmol/L) with a low-fat, MCT supplemented diet and moderate DHA supplementation.

Effect of optimal dietary therapy upon visual function in children with long-chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) and trifunctional protein (TFP) deficiency
(in Molecular Genetics and Metabolism) Melanie B. Gillingham PhD 1,2, Richard G. Weleber MD 2,3,5, Martha Neuringer PhD 3,4,5,6, William E. Connor MD 4, Monte Mills MD 7, Sandy van Calcar MS 8, James Verhoeve PhD 7, Jon Wolff MD 8 ,9 and Cary O. Harding MD 1,2

From the Departments of Pediatrics 1, Molecular and Medical Genetics 2, Ophthalmology 3 and Medicine 4, the Casey Eye Institute 5, and the Oregon National Primate Research Center 6 at Oregon Health & Science University, Portland, Oregon 97239 and from the Departments of Ophthalmology and Visual Sciences 7, The Waisman Center 8, and the Department of Pediatrics 9, University of Wisconsin Medical School, Madison, Wisconsin, 53705

Corresponding author and reprint requests to :
Melanie B. Gillingham, PhD, RD
Dietetics & Nutrition 
Mail Code: FM10 
3181 SW Sam Jackson Park Road 
Portland, OR 97239
Phone: (503) 494-1682 FAX: (503) 418-7076
Email: gillingm@ohsu.edu