Laboratory Diagnosis of a Case with Coenzyme Q10 Deficiency

Following an uneventful pregnancy, a boy was born from nonconsanguineous parents with no relevant family history. Within the first 24 hours after birth, he presented with cyanosis, lethargy, decreased spontaneous movements, hyperexcitability, and mild hypotonia. Under the suspicion of a mitochondrial disorder (MD), supplementation with different enzymatic cofactors was started, with no improvement. Refractory epilepsy, psychomotor delay, nystagmoid movements, and non-nephrotic range proteinuria were observed. The patient died at 9 months of age. Venous blood analysis showed lactic acidosis. Lactate was also increased in cerebrospinal fluid (CSF): 3.74 mmol/L (reference interval [RI]: 1.11–2.22 mmol/L)). Impaired mitochondrial metabolism was further suggested by an increase of plasma alanine (797 µmol/L, RI: 190–337 µmol/L), CSF alanine (81 µmol/L, RI: 12–52 µmol/L) and an abnormal urine organic acid profile (increased excretion of succinate, fumarate, and 2-oxoglutarate). Increased concentrations of fibroblast growth factor-21 (FGF-21) (952 ng/L, RI: 0–300 ng/L) were detected. Analysis of coenzyme Q10 (CoQ) by HPLC-electrochemical detection gave normal results in plasma, while a decrease in fibroblasts (36 nmol/g protein, RI: 91–151 nmol/g protein) and skeletal muscle was observed (56.2 nmol/g protein, RI: 110–480 nmol/g protein) (Fig. 1). The activity of mitochondrial respiratory chain (MRC) succinate-cytochrome c reductase in fibroblasts, which depends on CoQ status, was reduced (9.04 nmol/min/mg protein) when compared with a control line of neonatal fibroblasts analyzed in parallel (16.01 nmol/min/mg protein).

This work was supported by grants from the Instituto de Salud Carlos III (ISCIII-FIS PI17/00109 and PI17/01286). A.J. Paredes-Fuentes, a grant from the Instituto de Salud Carlos III (FI18/00253).