Coenzyme Q₁₀ (CoQ₁₀) is an essential lipid-soluble molecule that plays a central role in mitochondrial energy production as a mobile electron carrier. In addition to its bioenergetic function, CoQ₁₀ participates in antioxidant defense, redox homeostasis, lipid and nucleotide metabolism, and mitochondrial quality control. Primary CoQ₁₀ deficiencies are rare inherited mitochondrial disorders caused by pathogenic variants in nuclear genes involved in CoQ₁₀ biosynthesis. These defects lead to reduced CoQ₁₀ levels and impaired mitochondrial functions. Clinically, primary CoQ₁₀ deficiencies display remarkable phenotypic heterogeneity, ranging from isolated organ involvement, notably renal or cerebellar disease, to severe multisystemic disorders affecting the nervous system, skeletal muscle, heart, and other organs. Disease onset spans from the antenatal period to adulthood, and clinical severity varies widely, even among patients carrying variants in the same gene. This diversity cannot be fully explained by defective ATP production alone. Growing evidence indicates that disruption of non-bioenergetic functions of CoQ₁₀, including oxidative stress regulation and CoQ-dependent metabolic pathways, contributes significantly to disease pathophysiology and tissue vulnerability. In this review, we summarize current knowledge on CoQ₁₀ biology, biosynthesis, and the clinical spectrum of primary CoQ₁₀ deficiencies, and we discuss emerging mechanisms linking CoQ₁₀ depletion to mitochondrial dysfunctions and human diseases.

Three clinical entities of multiple acyl‐CoA dehydrogenase deficiency (MADD, OMIM#231680) can be differentiated: two severe neonatal forms and one later‐onset form that can manifest in adulthood. The latter typically presents with muscle‐related symptoms, such as exercise intolerance and muscle weakness, with an increase in all chain‐length acylcarnitine species on the acylcarnitine profile. Here, we report the case of a 33‐year‐old woman who experienced severe psychiatric issues complicated by an eating disorder resulting in a significant malnutrition a few months before presenting with a profound muscle weakness, fatigue, intermittent ptosis, and a major rhabdomyolysis (creatine kinase (CK) > 15 000 IU/L). Biochemical blood tests, including acylcarnitine profile, urinary organic acid analysis, and in vitro beta‐oxidation, were not suggestive of a metabolic disease. Given the absence of an etiology and the worsening health condition of the patient, whole exome sequencing (WES) was performed and revealed two pathogenic variants in the electron transfer flavoprotein dehydrogenase (ETFDH) gene, whose association has not been reported before. Unlike other beta oxidation deficiencies, which have a typical biochemical signature, the diagnosis of MADD was made by genetic analyses, which allowed the introduction of vitamin B2 supplementation and the rapid improvement of symptoms.

Romain Penicaud, Pharm.D., Mylene Gilleron, Ph.D. Pharm.D., Anne Frederique Dessein, Ph.D. Pharm.D., Dries Dobbelaere, M.D. and Marie Joncquel, Ph.D. Pharm.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2026.0120