Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q10 Biosynthesis Disorders

Azizia Wahedi; Sniya Sudhakar; Amanda Lam; Jose Ignacio Rodriguez Ciancio; Philippa Mills; Paul Gissen; Alice Gardham; Jogesh Kapadia; Jane Hassell; Simon Heales; Shamima Rahman

doi:10.1212/NXG.0000000000200209

Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q₁₀ Biosynthesis Disorders

Neurol Genet. 2024 Nov 25;10(6):e200209. doi: 10.1212/NXG.0000000000200209. eCollection 2024 Dec.

Affiliation

¹ From the Mitochondrial Research Group (A.W., S.R.), Genetics and Genomic Medicine Department, UCL Great Ormond Street Institute of Child Health, London; Medical Sciences Division (A.W.), University of Oxford; Department of Radiology (S.S.), Great Ormond Street Hospital for Children; Neurometabolic Unit (A.L., S.H.), National Hospital for Neurology and Neurosurgery; Department of Chemical Pathology, Great Ormond Street Hospital for Children; Neuromuscular Diseases (A.L.), Queen Square, UCL Institute of Neurology; Inborn Errors of Metabolism Section (J.I.R.C., P.M., S.H.), Genetics and Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health; National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre (P.G.), University College London; Metabolic Department (P.G., S.R.), Great Ormond Street Hospital for Children; North West Thames Regional Genetic Service (A.G.), North West London Hospitals; Neonatal Intensive Care Unit (J.K.), Luton and Dunstable University Hospital; and Department of Paediatric Neurology (J.H.), Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.

Abstract

Background and objectives: Disorders of coenzyme Q₁₀ (CoQ₁₀) biosynthesis comprise a group of 11 clinically and genetically heterogeneous rare primary mitochondrial diseases. We sought to delineate clinical, biochemical, and neuroimaging features of these disorders, together with outcomes after oral CoQ₁₀ supplementation and the utility of peripheral blood mononuclear cell (PBMNC) CoQ₁₀ levels in monitoring therapy.

Methods: This was a retrospective cohort study, registered as an audit at a specialist pediatric hospital (Registration Number: 3318) of 14 patients with genetically confirmed CoQ₁₀ biosynthesis deficiency, including 13 previously unreported cases.

Results: We show that oral doses of CoQ₁₀ up to 70 mg/kg/d were needed to ameliorate neurologic features. Additional idebenone was required to control seizures in some cases, and 3 children with neonatal-onset neurologic disease died in early childhood despite receiving high-dose oral CoQ₁₀ from birth. We also demonstrate that early diagnosis and treatment of CoQ₁₀ deficiency with oral supplementation (30 mg/kg/d) can reverse renal manifestations and can completely prevent kidney disease over 10 years of follow-up. PBMNC CoQ₁₀ levels increased after oral CoQ₁₀ supplementation, demonstrating absorption of exogenous CoQ₁₀ into the bloodstream.

Discussion: An early genome-wide diagnostic approach is needed for expeditious diagnosis of CoQ₁₀ biosynthesis disorder because our study demonstrates that there are no pathognomonic blood, muscle, or imaging biomarkers of these diseases. Our findings indicate that earlier diagnosis and treatment with high-dose CoQ₁₀ is key in halting progression of kidney disease or preventing it altogether. This study uses serial PBMNC CoQ₁₀ levels to monitor therapy. Patients with genetically confirmed CoQ₁₀ biosynthesis disorder should receive high-dose oral CoQ₁₀ as soon as possible after presentation, regardless of genetic cause, to prevent disease progression, but parents of children with neonatal or infantile neurologic presentations should be counseled about the poor prognosis.