ANALYSIS OF COQ SYNTHESIS USING LABELED NON RADIOACTIVE SUBSTRATES. APPLICATION FOR THE DIAGNOSIS OF PRIMARY COQ10 DEFICIENCIES.

Background: CoQ10 deficiencies are associated to mutations in genes of
CoQ biosynthesis and respond to CoQ10 supplementation. Early treatment
allows better outcome. Therefore, early diagnosis is desirable.
Objectives: Developing a non-radioactive methodology for fibroblast CoQ10
biosynthesis quantification that enables discriminating primary deficiencies.
Methods: Fibroblasts were incubated 72 h with 28 ?M 2 H3-mevalonate or
1.65 mM 13 C6-p-hydroxybenzoate. The labeled CoQ10 synthesized was
analyzed by HPLC-MS/MS.
Patients: A) To validate the method: one patient with confirmed primary
deficiency (COQ2 mutation) and 6 patients with CoQ10 deficiency secondary
to other inborn errors of metabolism (ETF, ETFDH, VLCAD, MELAS
or Nieman-Pick Type C).
B) 3 groups of CoQ10 deficiencies: 1) 3 Patients heterozygous for one COQ
gene; 2) 5 without mutations in the genes studied but responsive to CoQ10,
3) 9 clearly deficient, without further genetic or therapeutical studies.
Results and discussion: A) We have demonstrated that our method is
suitable for discriminating between primary and secondary deficiencies.
B) 10/17 patients' fibroblasts investigated showed significantly decreased
CoQ10 synthesis (40-88 % of the lower control) and mutational study of
COQ genes should be performed. In patients with normal rates the deficiency
is probably secondary.
Conclusions: Our method is a good tool for the diagnosis of these treatable
diseases.

Jaar van publicatie:2012

Trefwoorden:COQ synthesis, COQ10 deficiency