Docosahexaenoic acid therapy in peroxisomal diseases Results of a double-blind, randomized trial

University of Texas Medical Branch, Galveston, TX, USA.
Neurology (Impact Factor: 8.29). 08/2010; 75(9):826-30. DOI: 10.1212/WNL.0b013e3181f07061
Source: PubMed


Peroxisome assembly disorders are genetic disorders characterized by biochemical abnormalities, including low docosahexaenoic acid (DHA). The objective was to assess whether treatment with DHA supplementation would improve biochemical abnormalities, visual function, and growth in affected individuals.
This was a randomized, double-blind, placebo-controlled trial conducted at a single center. Treatment groups received supplements of DHA (100 mg/kg per day). The primary outcome measures were the change from baseline in the visual function and physical growth during the 1 year follow-up period.
Fifty individuals were enrolled and randomized. Two were subsequently excluded from study analysis when it was determined that they had a single enzyme disorder of peroxisomal beta oxidation. Thirty-four returned for follow-up. Nine patients died during the trial of their disorder, and 5 others were lost to follow-up. DHA supplementation was well tolerated. There was no difference in the outcomes between the treated and untreated groups in biochemical function, electroretinogram, or growth. Improvements were seen in both groups in certain individuals.
DHA supplementation did not improve the visual function or growth of treated individuals with peroxisome assembly disorders. Classification of evidence: This interventional study provides Class II evidence that DHA supplementation did not improve the visual function or growth of treated individuals with peroxisome assembly disorders during an average of 1 year of follow-up in patients aged 1 to 144 months.

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Available from: Linah Albanna, Aug 18, 2014
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    • "Currently, there is no cure for ZSDs and possibilities for supportive and symptomatic treatment are limited. Some patients received docosahexaenoic acid without any proven positive effect [25]. In addition, some patients follow a phytanic acid reduced diet and are supplemented with fat-soluble vitamins [26]. "
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    ABSTRACT: Zellweger spectrum disorders (ZSDs) are multisystem genetic disorders caused by a lack of functional peroxisomes, due to mutations in one of the PEX genes, encoding proteins involved in peroxisome biogenesis. The phenotypic spectrum of ZSDs ranges from an early lethal form to much milder presentations. In cultured skin fibroblasts from mildly affected patients, peroxisome biogenesis can be partially impaired which results in a mosaic catalase immunofluorescence pattern. This peroxisomal mosaicism has been described for specific missense mutations in various PEX genes. In cell lines displaying peroxisomal mosaicism, peroxisome biogenesis can be improved when these are cultured at 30[degree sign]C. This suggests that these missense mutations affect the folding and/or stability of the encoded protein. We have studied if the function of mutant PEX1, PEX6 and PEX12 can be improved by promoting protein folding using the chemical chaperone arginine. Fibroblasts from three PEX1 patients, one PEX6 and one PEX12 patient were cultured in the presence of different concentrations of arginine. To determine the effect on peroxisome biogenesis we studied the following parameters: number of peroxisome-positive cells, levels of PEX1 protein and processed thiolase, and the capacity to beta-oxidize very long chain fatty acids and pristanic acid. Peroxisome biogenesis and function in fibroblasts with mild missense mutations in PEX1, 6 and 12 can be improved by arginine. Arginine may be an interesting compound to promote peroxisome function in patients with a mild peroxisome biogenesis disorder.
    Full-text · Article · Sep 2013 · Orphanet Journal of Rare Diseases
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    • "Increases of the DHA pool and improves visual functions. Paker et al. 2010 (44) Double-blind, placebo- controlled randomized trial 50 children with peroxisomal disorders (1 months-10y) "
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    ABSTRACT: A number of studies are investigating the role of n-3 polyunsaturated fatty acids in children with metabolic inborn errors, while the effects on visual and brain development in premature infants and neonates are well known. However, their function incertain chronic neurological, inflammatory and metabolic disorders is still under study. Standards should be established to help identify the need of docosahexaenoic acid supplementation in conditions requiring a restricted diet resulting in an altered metabolism system, and find scientific evidence on the effects of such supplementation. This study reviews relevant published literature to propose adequate n-3 intake or supplementation doses for different ages and pathologies. The aim of this review is to examine the effects of long chain polyunsaturated fatty acids supplementation in preventing cognitive impairment or in retarding its progress, and to identify nutritional deficiencies, in children with inborn errors of metabolism. Trials were identified from a search of the Cochrane and MEDLINE databases in 2011. These databases include all major completed and ongoing double-blind, placebo-controlled, randomized trials, as well as all studies in which omega-3 supplementation was administered to children with inborn errors, and studies assessing omega-3 fatty acids status in plasma in these pathologies. Although few randomized controlled trials met the inclusion criteria of this review, some evidenced that most of children with inborn errors are deficient in omega-3 fatty acids, and demonstrated that supplementation might improve their neural function, or prevent the progression of neurological impairment. Nontheless, further investigations are needed on this issue.
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    ABSTRACT: Much has been learned about the group of peroxisomal disorders in recent years. This includes the development of sensitive laboratory methods allowing the measurement of the full panel of peroxisomal metabolites and follow-up enzymatic methods to pinpoint the underlying defect. Furthermore, the molecular basis of most—if not all—of the peroxisomal diseases identified so far has been resolved with obvious consequences for diagnosis including prenatal diagnosis. The availability of these sophisticated and sensitive methods together with the rapid development of genetic techniques including whole exome and genome sequencing has allowed the identification of atypical phenotypes including isolated cerebellar ataxia, a.o. which holds great promises for the future in terms of patient recognition. This is especially important since therapeutic measures will surely become available in the next years to come, surely for the milder variants.
    No preview · Article · Jan 2013
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