Dataset Information

Coenzyme Q10 and Pyridoxal Phosphate Deficiency Is a Common Feature in Mucopolysaccharidosis Type III.

ABSTRACT: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiencies of lysosomal enzymes catalyzing degradation of glycosaminoglycans (GAGs). Previously, we reported a secondary plasma coenzyme Q10 (CoQ) deficiency in MPS patients. For this study, nine MPS patients were recruited in the Hospital Sant Joan de Déu (HSJD, Barcelona) and two patients in the Neurometabolic Unit, National Hospital (NMU, London), to explore the nutritional status of MPS type III patients by analyzing several vitamins and micronutrients in blood and in cerebrospinal fluid. Plasma CoQ and plasma and cerebrospinal fluid pyridoxal phosphate (PLP) content were analyzed by high-pressure liquid chromatography (HPLC) with electrochemical and fluorescence detection, respectively. We found that most MPS-III patients disclosed low plasma pyridoxal phosphate (PLP) values (seven out of nine) and also low plasma CoQ concentrations (eight out of nine). We observed significantly lower median values of PLP, tocopherol, and CoQ (Mann-Whitney U test, p?=?0.006, p?=?0.004, and p?= 0.001, respectively) in MPS patients when compared with age-matched controls. Chi-square test showed a significant association between the fact of having low plasma PLP and CoQ values in the whole cohort of patients. Cerebrospinal fluid PLP values were clearly deficient in the two patients studied. In conclusion, we report a combined CoQ and PLP deficiency in MPS-III patients. These observations could be related to the complexity of the physiopathology of the disease. If our results are confirmed in larger series of patients, CoQ and PLP therapy could be trialed as coadjuvant therapy with the current MPS treatments.

SUBMITTER: Yubero D

PROVIDER: S-EPMC5059182 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Coenzyme Q<sub>10</sub> and Pyridoxal Phosphate Deficiency Is a Common Feature in Mucopolysaccharidosis Type III.

Yubero Dèlia D Montero Raquel R O'Callaghan Mar M Pineda Mercè M Meavilla Silvia S Delgadillo Veronica V Sierra Cristina C Altimira Laura L Navas Plácido P Pope Simon S Oppenheim Marcus M Neergheen Viruna V Ghosh Arunabha A Mills Phillipa P Clayton Peter P Footitt Emma E Cleary Maureen M Hargreaves Iain I Jones Simon A SA Heales Simon S Artuch Rafael R

JIMD reports 20150724

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiencies of lysosomal enzymes catalyzing degradation of glycosaminoglycans (GAGs). Previously, we reported a secondary plasma coenzyme Q<sub>10</sub> (CoQ) deficiency in MPS patients. For this study, nine MPS patients were recruited in the Hospital Sant Joan de Déu (HSJD, Barcelona) and two patients in the Neurometabolic Unit, National Hospital (NMU, London), to explore the nutritional status of MPS type III pat ...[more]

PMID: 26205433

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Project description:Coenzyme Q10 (CoQ10) deficiency syndrome is a rare condition that causes mitochondrial dysfunction and includes a variety of clinical presentations as encephalomyopathy, ataxia and renal failure. First, we sought to set up what all have in common, and then investigate why CoQ10 supplementation reverses the bioenergetics alterations in cultured cells but not all the cellular phenotypes. DESIGN MODELLING STUDY: This work models the transcriptome of human CoQ10 deficiency syndrome in primary fibroblast from patients and study the genetic response to CoQ10 treatment in these cells.Four hospitals and medical centres from Spain, Italy and the USA, and two research laboratories from Spain and the USA.Primary cells were collected from patients in the above centres.We characterised by microarray analysis the expression profile of fibroblasts from seven CoQ10-deficient patients (three had primary deficiency and four had a secondary form) and aged-matched controls, before and after CoQ10 supplementation. Results were validated by Q-RT-PCR. The profile of DNA (CpG) methylation was evaluated for a subset of gene with displayed altered expression.CoQ10-deficient fibroblasts (independently from the aetiology) showed a common transcriptomic profile that promotes cell survival by activating cell cycle and growth, cell stress responses and inhibiting cell death and immune responses. Energy production was supported mainly by glycolysis while CoQ10 supplementation restored oxidative phosphorylation. Expression of genes involved in cell death pathways was partially restored by treatment, while genes involved in differentiation, cell cycle and growth were not affected. Stably demethylated genes were unaffected by treatment whereas we observed restored gene expression in either non-methylated genes or those with an unchanged methylation pattern.CoQ10 deficiency induces a specific transcriptomic profile that promotes cell survival, which is only partially rescued by CoQ10 supplementation.

Dataset Information

Coenzyme Q10 and Pyridoxal Phosphate Deficiency Is a Common Feature in Mucopolysaccharidosis Type III.

Publications

Coenzyme Q<sub>10</sub> and Pyridoxal Phosphate Deficiency Is a Common Feature in Mucopolysaccharidosis Type III.

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