TY - JOUR
T1 - Effect of optimal dietary therapy upon visual function in children with long-chain 3-hydroxyacyl CoA dehydrogenase and trifunctional protein deficiency
AU - Gillingham, Melanie B.
AU - Weleber, Richard G.
AU - Neuringer, Martha
AU - Connor, William E.
AU - Mills, Monte
AU - Van Calcar, Sandy
AU - Ver Hoeve, James
AU - Wolff, Jon
AU - Harding, Cary O.
N1 - Funding Information:
We thank Dr. Arnold Strauss (Vanderbilt University, Nashville, TN) for providing the mutation analysis results of subjects not available in the medical record, and Melissa Krahmer and Andrea Billingslea for assistance with ERG and acuity testing. We thank Sara Wilson for her assistance with preparation of the manuscript. This research was supported by PHS Grants 5 MO1 RR00334 and RR03186. Post-doctoral training for MB Gillingham was supported by PHS Grant T32GM08796 and by the Doernbecher Foundation. Martek Biosciences Corporation supplied the DHA supplements (DHASCO). R.G.W. and M.N. were supported in part from grants from The Foundation Fighting Blindness, Owings Mills, MD, and Research to Prevent Blindness, New York, NY.
PY - 2005/9
Y1 - 2005/9
N2 - The objective of this prospective cohort study was to determine if dietary therapy including docosahexaenoic acid (DHA; C22:6ω-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 β-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.
AB - The objective of this prospective cohort study was to determine if dietary therapy including docosahexaenoic acid (DHA; C22:6ω-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 β-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.
KW - Chorioretinopathy
KW - Docosahexaenoic acid
KW - Hydroxyacylcarnitines
KW - Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
KW - Trifunctional protein deficiency
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U2 - 10.1016/j.ymgme.2005.06.001
DO - 10.1016/j.ymgme.2005.06.001
M3 - Article
C2 - 16040264
AN - SCOPUS:26244444855
SN - 1096-7192
VL - 86
SP - 124
EP - 133
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1-2
ER -