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.

Dystonia-Ataxia with early handwriting deterioration in COQ8A mutation carriers: A case series and literature review / Galosi, S.; Barca, E.; Carrozzo, R.; Schirinzi, T.; Quinzii, C. M.; Lieto, M.; Vasco, G.; Zanni, G.; Di Nottia, M.; Galatolo, D.; Filla, A.; Bertini, E.; Santorelli, F. M.; Leuzzi, V.; Haas, R.; Hirano, M.; Friedman, J.. - In: PARKINSONISM & RELATED DISORDERS. - ISSN 1353-8020. - 68:(2019), pp. 8-16. [10.1016/j.parkreldis.2019.09.015]

Dystonia-Ataxia with early handwriting deterioration in COQ8A mutation carriers: A case series and literature review

Galosi S.
Primo
Writing – Original Draft Preparation
;
Bertini E.;Santorelli F. M.;Leuzzi V.;
2019

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.
2019
COQ8A; CoQ; 10; deficiency; Dystonia-ataxia syndrome; Handwriting deterioration; Adult; Child; Female; Humans; Male; Middle Aged; Mitochondrial Proteins; Ubiquinone; Young Adult; Ataxia; Disease Progression; Dystonic Disorders; Handwriting; Heterozygote; Mitochondrial Diseases; Muscle Weakness
01 Pubblicazione su rivista::01g Articolo di rassegna (Review)
Dystonia-Ataxia with early handwriting deterioration in COQ8A mutation carriers: A case series and literature review / Galosi, S.; Barca, E.; Carrozzo, R.; Schirinzi, T.; Quinzii, C. M.; Lieto, M.; Vasco, G.; Zanni, G.; Di Nottia, M.; Galatolo, D.; Filla, A.; Bertini, E.; Santorelli, F. M.; Leuzzi, V.; Haas, R.; Hirano, M.; Friedman, J.. - In: PARKINSONISM & RELATED DISORDERS. - ISSN 1353-8020. - 68:(2019), pp. 8-16. [10.1016/j.parkreldis.2019.09.015]
File allegati a questo prodotto
File Dimensione Formato  
Galosi_Dystonia-Ataxia_2019.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 786.21 kB
Formato Adobe PDF
786.21 kB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1517200
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 14
social impact