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; C22:6ω-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 (R max ) (p=0.0038, R 2 =0.62). In addition, subjects with sustained low plasma long-chain NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 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, R 2 =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.

Ocular characteristics in 10 children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: a cross-sectional study with long-term follow-up

“…In the present study, half of the patients initially demonstrated subtle general pigmentations spread in the posterior poles and in the mid-periphery and not in the macular areas, a finding also described by Gillingham et al (2005). In the children with macular pigmentations, the darker appearance of the macular region may be partly the result of perimacular atrophy, which increases the contrast to the surrounding retina.…”

Effects of higher dietary protein intake on energy balance and metabolic control in children with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency

“…The sum of long-chain hydroxyacylcarnitine concentrations, a measure of partial fatty acid oxidation metabolites in subjects with LCHAD or TFP deficiency and an indicator of metabolic control, did show a non-significant trend toward increased levels in the fasting state but postprandial AUC levels were not different. A rise in hydroxyacylcarnitine concentrations with a high protein diet could be detrimental to long-term outcomes even if it prevents obesity [8]. Further long-term study is needed to determine the metabolic safety of a high-protein diet in individuals with fatty acid oxidation disorders.…”

“…Nine subjects, seven years of age or older, with a conWrmed diagnosis of LCHAD or TFP deficiency were recruited from a previous cohort for this study [7,8]. Six cases had previously published mutation analyses [9][10][11][12].…”

Mikroglia und Immuntherapien bei degenerativen Netzhauterkrankungen

“…Der Erhalt des Gesichtsfelds war dabei direkt mit der Normalisierung des DHASpiegels im Blut korreliert. Ähnlich dazu korrelieren hohe Plasma-DHA-Konzentrationen nach Nahrungsergänzung mit dem Erhalt der Netzhautfunktion und Sehschärfe bei Kindern mit langkettiger 3-Hydroxyacyl-CoA-Dehydrogenasedefizienz [22] …”