Decreased plasma ubiquinone-10 concentration in patients with mevalonate kinase deficiency.

Détails

ID Serval
serval:BIB_7B4F41522E66
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Decreased plasma ubiquinone-10 concentration in patients with mevalonate kinase deficiency.
Périodique
Pediatric Research
Auteur⸱e⸱s
Hübner C., Hoffmann G.F., Charpentier C., Gibson K.M., Finckh B., Puhl H., Lehr H.A., Kohlschütter A.
ISSN
0031-3998 (Print)
ISSN-L
0031-3998
Statut éditorial
Publié
Date de publication
1993
Volume
34
Numéro
2
Pages
129-133
Langue
anglais
Résumé
Patients with mevalonate kinase deficiency suffer from psychomotor retardation, ataxia with progredient cerebellar atrophy, and myopathy. The pathophysiology of the disease remains unclear. The mevalonate kinase product, cholesterol, is within the normal range in patient plasma and fibroblasts. In search of the pathophysiology of this disorder, another mevalonate kinase product, ubiquinone-10, was studied. The concentrations of ubiquinone-10 in patient plasma (n = 6) and ubiquinol-10 in patient LDL (n = 2) and the synthesis of ubiquinone-10 in patient fibroblasts (n = 4) were determined. After oxidative modification of LDL by copper in vitro, the concentrations of alpha-tocopherol and polyunsaturated fatty acids in LDL and the relative electrophoretic mobility of LDL were measured to determine the antioxidant capacity of LDL samples of two affected siblings. The ubiquinone-10 concentrations in plasma samples (median = 508 micrograms/L, range = 488-642 micrograms/L) versus controls (median = 613 micrograms/L, range = 564-809 micrograms/L; p < 0.005) were decreased. In LDL samples of two affected siblings, the concentration of ubiquinol-10 and the resistance to oxidation in vitro were found decreased during intercurrent patient crisis condition. In patient fibroblasts (median = 533 dpm/mg protein, range = 399-1,047 dpm/mg protein) versus controls (median = 40,731 dpm/mg protein, range = 12,774-54,739 dpm/mg protein), the synthesis of ubiquinone was found to be decreased. We conclude that mevalonate kinase deficiency leads to a decreased synthesis of ubiquinone-10 and that ubiquinone-10 deficiency is responsible for the clinical progression of this disease characterized by increased lipid peroxidation, cerebellar atrophy, cataract development, and myopathy with increased creatine kinase activity.
Mots-clé
Cells, Cultured, Child, Child, Preschool, Creatine Kinase/blood, Dolichol/metabolism, Female, Fibroblasts/metabolism, Humans, Infant, Lipoproteins, LDL/blood, Male, Metabolism, Inborn Errors/drug therapy, Metabolism, Inborn Errors/metabolism, Mevalonic Acid/blood, Mevalonic Acid/urine, Oxidation-Reduction, Phosphotransferases (Alcohol Group Acceptor)/deficiency, Ubiquinone/biosynthesis, Ubiquinone/blood, Vitamin E/blood, Vitamin E/therapeutic use
Pubmed
Création de la notice
25/11/2011 20:08
Dernière modification de la notice
20/08/2019 15:37
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