{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T20:00:46Z","timestamp":1788897646016,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,6,18]],"date-time":"2013-06-18T00:00:00Z","timestamp":1371513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Primary coenzyme Q<jats:sub>10<\/jats:sub> (CoQ<jats:sub>10<\/jats:sub>) deficiencies are associated with mutations in genes encoding enzymes important for its biosynthesis and patients are responsive to CoQ<jats:sub>10<\/jats:sub> supplementation. Early treatment allows better prognosis of the disease and therefore, early diagnosis is desirable. The complex phenotype and genotype and the frequent secondary CoQ<jats:sub>10<\/jats:sub> deficiencies make it difficult to achieve a definitive diagnosis by direct quantification of CoQ<jats:sub>10<\/jats:sub>. We developed a non\u2010radioactive methodology for the quantification of CoQ<jats:sub>10<\/jats:sub> biosynthesis in fibroblasts that allows the identification of primary deficiencies. Fibroblasts were incubated 72 h with 28 \u03bcmol\/L <jats:sup>2<\/jats:sup>H<jats:sub>3<\/jats:sub>\u2010mevalonate or 1.65 mmol\/L <jats:sup>13<\/jats:sup>C<jats:sub>6<\/jats:sub>\u2010p\u2010hydroxybenzoate. The newly synthesized <jats:sup>2<\/jats:sup>H<jats:sub>3<\/jats:sub>\u2010 and <jats:sup>13<\/jats:sup>C<jats:sub>6<\/jats:sub>\u2010 labelled CoQ<jats:sub>10<\/jats:sub> were analysed by high performance liquid chromatography\u2010tandem mass spectrometry. The mean and the reference range for <jats:sup>13<\/jats:sup>C<jats:sub>6<\/jats:sub>\u2010CoQ<jats:sub>10<\/jats:sub> and <jats:sup>2<\/jats:sup>H<jats:sub>3<\/jats:sub>\u2010CoQ<jats:sub>10<\/jats:sub> biosynthesis were 0.97 (0.83\u20131.1) and 0.13 (0.09\u20130.17) nmol\/Unit of citrate synthase, respectively. We validated the methodology through the study of one patient with <jats:italic>COQ2<\/jats:italic> mutations and six patients with CoQ<jats:sub>10<\/jats:sub> deficiency secondary to other inborn errors of metabolism. Afterwards we investigated 16 patients\u2019 fibroblasts and nine showed decreased CoQ<jats:sub>10<\/jats:sub> biosynthesis. Therefore, the next step is to study the COQ genes in order to reach a definitive diagnosis in these nine patients. In the patients with normal rates the deficiency is probably secondary. In conclusion, we have developed a non\u2010invasive non\u2010radioactive method suitable for the detection of defects in CoQ<jats:sub>10<\/jats:sub> biosynthesis, which offers a good tool for the stratification of patients with these treatable mitochondrial diseases.<\/jats:p>","DOI":"10.1007\/s10545-013-9620-4","type":"journal-article","created":{"date-parts":[[2013,6,17]],"date-time":"2013-06-17T07:24:14Z","timestamp":1371453854000},"page":"53-62","source":"Crossref","is-referenced-by-count":26,"title":["Characterization of CoQ<sub>10<\/sub> biosynthesis in fibroblasts of patients with primary and secondary CoQ<sub>10<\/sub> deficiency"],"prefix":"10.1002","volume":"37","author":[{"given":"Nuria","family":"Buj\u00e1n","sequence":"first","affiliation":[{"name":"Secci\u00f3 d'Errors Cong\u00e8nits del Metabolisme\u2010IBC, Servei de Bioqu\u00edmica i Gen\u00e8tica Molecular Hospital Cl\u00ednic, CIBERER Edifici Helios III, planta baixa, C\/Mej\u00eda Lequerica s\/n Barcelona 08028 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