Category: Ataxia
Objective: To report a case of Coenzyme Q10 (CoQ10) deficiency due to COQ4 variants causing adult-onset ataxia and dystonic postures.
Background: CoQ10 is an essential component of the mitochondrial electron transport chain. Eleven distinct genes are responsible for encoding proteins of CoQ10 biosynthesis. COQ4 encodes a protein involved in organizing a multi-enzyme complex required for this process. Bi-allelic variants have been associated with different phenotypes as infantile mitochondrial multi-organ disorder, childhood-onset ataxia with stroke-like episode and neonatal lethal encephalopathy, but also recent described adult-onset spastic paraparesis and/or cerebellar ataxia.
Method: Case Report.
Results: A 37-year-old Brazilian woman, started at age of 18 years, with hand and head tremor, with dystonic component and frequent falls. These symptoms worsened in a slowly progressive fashion, starting with and after some years of disease her gait became clearly unsteady. She never had any visual or hearing impairment, dysphagia, urinary dysfunction or signs of neuropathy. Regarding her family history, she is the younger daughter of healthy parents, being first-degree cousins, with her only brother presenting with similar symptoms and evolution. On neurological exam, she presented with mild dysarthria, nystagmus evoked on horizontal and vertical gazes, with phase change, hypometric saccades, but without ophthalmoparesis, ataxic gait, cervical dystonic tremor with a no-no component and left torticollis and appendicular dystonic posture. Reflexes were normal, Babinski was negative. A wide laboratory investigation was unremarkable and brain MRI disclosed cerebellar atrophy, with no significant white matter changes. Her ophthalmological exam was unremarkable. Genetic testing for Friedreich’s Ataxia was negative, and her whole exome sequencing disclosed homozygous COQ4 variant (COQ4:c.202+4A>C). The patient has received coenzyme Q 10 since then, with slight improvement in gait, as well as botulinum toxin for cervical dystonia.
Conclusion: The investigation of adult-onset ataxia can be broad, but identifying the genetic defect in patients with hereditary movement disorders is crucial not only for patient counseling, but also in terms of emerging therapeutic options. COQ4, and possibly also other genes involved in CoQ10 biosynthesis, represent this expanding group.
References: 1. CORDTS. I. et al. Bi-Allelic COQ4 Variants Cause Adult-Onset Ataxia-Spasticity Spectrum Disease. Movement Disorders, Vol. 37, No. 10, 2022
2. BREA-CALVO, G. et al. COQ4 Mutations Cause a Broad Spectrum of Mitochondrial Disorders Associated with CoQ10 Deficiency. The American Journal of Human Genetics 96, 309–317, February 5, 2015
3. LAUGWITZ, L. et al. Human COQ4 deficiency: delineating the clinical, metabolic and neuroimaging phenotypes. J Med Genet. 2022 September ; 59(9): 878–887
To cite this abstract in AMA style:
T. Coradine, M. Soares, P. Fraiman, L. Corazza, T. Silva, J. Pedroso, O. Barsottini. An Unusual and Treatable Cause of Cerebellar Ataxia and Dystonia: Homozygous COQ4 Gene Mutation [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/an-unusual-and-treatable-cause-of-cerebellar-ataxia-and-dystonia-homozygous-coq4-gene-mutation/. Accessed October 4, 2024.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/an-unusual-and-treatable-cause-of-cerebellar-ataxia-and-dystonia-homozygous-coq4-gene-mutation/