Plasma coenzyme Q10 status is impaired in selected genetic conditions

Abstract

Identifying diseases displaying chronic low plasma Coenzyme Q₁₀ (CoQ) values may be important to prevent possible cardiovascular dysfunction. The aim of this study was to retrospectively evaluate plasma CoQ concentrations in a large cohort of pediatric and young adult patients. We evaluated plasma CoQ values in 597 individuals (age range 1 month to 43 years, average 11 years), studied during the period 2005-2016. Patients were classified into 6 different groups: control group of healthy participants, phenylketonuric patients (PKU), patients with mucopolysaccharidoses (MPS), patients with other inborn errors of metabolism (IEM), patients with neurogenetic diseases, and individuals with neurological diseases with no genetic diagnosis. Plasma total CoQ was measured by reverse-phase high-performance liquid chromatography with electrochemical detection and ultraviolet detection at 275 nm. ANOVA with Bonferroni correction showed that plasma CoQ values were significantly lower in the PKU and MPS groups than in controls and neurological patients. The IEM group showed intermediate values that were not significantly different from those of the controls. In PKU patients, the Chi-Square test showed a significant association between having low plasma CoQ values and being classic PKU patients. The percentage of neurogenetic and other neurological patients with low CoQ values was low (below 8%). In conclusión, plasma CoQ monitoring in selected groups of patients with different IEM (especially in PKU and MPS patients, but also in IEM under protein-restricted diets) seems advisable to prevent the possibility of a chronic blood CoQ suboptimal status in such groups of patients.

Figure 1

Typical chromatograms (HPLC with electrochemical detection) from: Left panel. Commercial control (Coenzyme Q₁₀ Chromsystens, level 1 (Ref. 0092): CoQ₁₀ = 0.56 µmol/L), based on serum matrix. Middle panel. Human plasma sample with CoQ₁₀ = 1.18 µmol/L. Right panel. Human plasma sample with CoQ₁₀ = 0.38 µmol/L. Samples, calibrators and controls are spiked with internal standard (Coenzyme Q₉ (CoQ₉)).

Figure 2

Box plot representation of: Left panel. Plasma CoQ values (µmol/L) in the 6 subject groups. Middle panel. Serum Chol (mmol/L) and Right panel CoQ/Chol values (µmol CoQ/mol Chol) from controls, PKU, MPS and IEM patients. Low plasma CoQ concentrations are frequently observed in both PKU and MPS patients, while the IEM group show intermediate values. The length of the boxes indicates the interquartile space (p25–p75); the horizontal line into the box represents the median (p50), and the circles indicate outlier values. *X-axis groups: Group 1: healthy participants. Group 2: phenylketonuric. Group 3: patients with mucopolysaccharidoses. Group 4: patients with other inborn errors of metabolism. Group 5: patients with neurogenetic diseases. Group 6: individuals with neurological diseases with no genetic diagnosis.

Figure 3

Graphic resprsentation of the assigned value (AV) study results in PKU patients. The black bars represent the number of PKU paints displaying low plasma CoQ concentrations in the different AV groups. The grey bars represent the number of PKU patients with normal plasma CoQ concentration. In AV groups 2 and 5 (classic PKU), the number of cases displaying low plasma CoQ values is higher than those belonging to AV groups 8 and 9 (milder PKU forms).