Dystonia-Ataxia with early handwriting deterioration in COQ8A mutation carriers: A case series and literature review. (November 2019)

• Record Type: Journal Article
• Authors: Galosi, Serena; Barca, Emanuele; Carrozzo, Rosalba; Schirinzi, Tommaso; Quinzii, Catarina Maria; Lieto, Maria; Vasco, Gessica; Zanni, Ginevra; Di Nottia, Michela; Galatolo, Daniele; Filla, Alessandro; Bertini, Enrico; Santorelli, Filippo Maria; Leuzzi, Vincenzo; Haas, Richard; Hirano, Michio; Friedman, Jennifer
• Is Part Of: Parkinsonism & related disorders. Volume 68(2019)
• Page Start: 8
• Page End: 16
• Publication Date: 2019-11
• Subjects: COQ8A -- CoQ10 deficiency -- Handwriting deterioration -- Dystonia-ataxia syndrome; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2019.09.015
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: Cerebellar ataxia is a hallmark of coenzyme Q10 (CoQ10 ) deficiency associated with COQ8A mutations. We present four patients, one with novel COQ8A pathogenic variants all with early, prominent handwriting impairment, dystonia and only mild ataxia. To better define the phenotypic spectrum and course of COQ8A disease, we review the clinical presentation and evolution in 47 reported cases. Individuals with COQ8A mutation display great clinical variability and unpredictable responses to CoQ10 supplementation. Onset is typically during infancy or childhood with ataxic features associated with developmental delay or regression. When disease onset is later in life, first symptoms can include: incoordination, epilepsy, tremor, and deterioration of writing. The natural history is characterized by a progression to a multisystem brain disease dominated by ataxia, with disease severity inversely correlated with age at onset. Six previously reported cases share with ours, a clinical phenotype characterized by slowly progressive or static writing difficulties, focal dystonia, and speech disorder, with only minimal ataxia. The combination of writing difficulty, dystonia and ataxia is a distinctive constellation that is reminiscent of a previously described clinical entity called Dystonia Ataxia Syndrome (DYTCA) and is an important clinical indicator of COQ8A mutations, even when ataxia is mild or absent. Highlights: Four new patients with COQ8A pathogenic variants. Prominent handwriting impairment, dystonia and mild ataxia as core clinical features. Six out of 47 previously reported cases share with ours this clinical phenotype. Dystonia-Ataxia with writing deterioration as clinical indicator of COQ8A mutations.