Long-Chain Polyunsaturated Fatty Acids in Inborn Errors of Metabolism

Abstract

The treatment of children with inborn errors of metabolism (IEM) is mainly based on restricted dietary intake of protein-containing foods. However, dietary protein restriction may not only reduce amino acid intake, but may be associated with low intake of polyunsaturated fatty acids as well. This review focuses on the consequences of dietary restriction in IEM on the bioavailability of long-chain polyunsaturated fatty acids (LCPUFAs) and on the attempts to ameliorate these consequences. We were able to identify during a literature search 10 observational studies investigating LCPUFA status in patients with IEM and six randomized controlled trials (RCTs) reporting effect of LCPUFA supplementation to the diet of children with IEM. Decreased LCPUFA status, in particular decreased docosahexaenoic acid (DHA) status, has been found in patients suffering from IEM based on the evidence of observational studies. LCPUFA supplementation effectively improves DHA status without detectable adverse reactions. Further research should focus on functional outcomes of LCPUFA supplementation in children with IEM.

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

“…For example, several mitochondrial disorders may result in increased oxidative stress and thereby increased peroxidation of omega-3 fatty acids (Gardner and Boles 2011). The precise (long-term) clinical consequences of these findings have yet to be further elucidated (Fekete and Decsi 2010;Gil-Campos and Sanjurjo Crespo 2012;Lohner et al 2013). …”

“…F a t t ya c i d sm a yp l a ya ni m p o r t a n tr o l ei ns e v e r a li n b o r n errors of metabolism. A full review of the different potential roles of fatty acids in these diseases exceeds the scope of this review, while earlier reviews are available (Fekete and Decsi 2010;Gil-Campos and Sanjurjo Crespo 2012;Lohner et al 2013). In brief, first, several inborn errors of metabolism require a restricted diet (e.g., phenolketonuria and organic acidaemias), potentially leading to fatty acid deficiencies.…”

Polyunsaturated fatty acid status in treated isovaleric acidemia patients

“…Nevertheless, our data are in good agreement with those in previous reports, which studied patients with various defects of amino acid metabolism, including the urea cycle defects. 5,6 CONCLUSIONS The proposed PUFA deficiency (indicated by a significantly increased individual PUFAS as well as the omega-6/omega-3 fatty acid ratio) was evident in treated IVA patients. We suggest that dietary supplementation of docosahexaenoic acid and arachidonic acid may be required to overcome nutritional deficiencies imposed by the protein-restricted diet prescribed to IVA patients.…”

“…Individuals with similar amino acid disorders have shown nutritional deficiencies. 6 We compared the PUFA profiles of 10 genetically homogeneous IVA patients with control subjects and found a significant reduction in all the individual omega-3 fatty acids in the IVA patient group. Significant deficiencies in individual PUFAs were found in the omega-6 and omega-9 fatty acid classes, with the exception of C18:2n-6, C18:3n-6, C20:2n-6, C22:4n-6, C16:1n-9, C18:1n-9 and 24:1n-9.…”

“…1,3 Related deficiency, more specifically in EFAs and consequently polyunsaturated fatty acid (PUFAs), has been described in patients with phenylketonuria, urea cycle defects, maple syrup urine disease, methylmalonic acidemia and homocystinuria. [3][4][5][6] The latter may therefore be considered as candidate-causing factors for the development of neurocognitive disturbances in IVA patients following a lowprotein diet, without notable nutrient supplementation.…”