| Autor: |
Ng, YS, Martikainen, M, Gorman, G, Blain, A, Bugiardini, E, Bunting, A, Schaefer, A, Alston, CL, Blakely, EL, Hughes, I, Lim, A, Degoede, C, McEntagart, M, Spinty, S, Horrocks, I, Chinnery, P, Horvath, R, Nesbitt, V, Fratter, C, Poulton, J, Hanna, M, Pitceathly, R, Taylor, RW, Turnbull, D, McFarland, R |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Popis: |
Importance: Mutations in the mitochondrial MT-ATP6 gene are an important cause of mitochondrial disease. Phenotypes related to these mutations include Leigh syndrome (LS), and the syndrome of neuropathy, ataxia, and retinitis pigmentosa (NARP); however, there are also reports of other and intermediate phenotypes. Objective: To characterise the phenotypic and genotypic spectrum of the MT-ATP6 related mitochondrial disease in a large and well-defined mitochondrial disease cohort. Design: A retrospective, observational cohort study. Setting: Three national diagnostic and clinical centres for mitochondrial disorders in Newcastle upon Tyne, Oxford and London; patients were recruited to the Mitochondrial Disease Patient Cohort, UK. Participants: Eighty-eight patients with clinically and genetically defined mitochondrial disease due to mutations in the MT-ATP6 gene that were included in this study. Data from 36 clinically unaffected carriers of MT-ATP6 mutations were also analysed. Main Outcomes and Measures: All patients were interviewed and examined. All available medical notes and clinical, radiological, and genetic investigations were reviewed. Results: We identified 88 clinically affected individuals and 36 asymptomatic family members from 60 pedigrees. Among the patients of whom the respective data were available, 57 of 69 (83%) had cerebellar ataxia, 42 of 57 (74%) had peripheral neuropathy, and 40 of 59 (68%) had some degree of cognitive dysfunction or learning disability. Thirty-two patients (36%) had a presentation compatible with LS, whereas just seven patients (8%) had the complete neuropathy, ataxia, and retinitis pigmentosa phenotype without LS. We observed meaningful differences between the clinical features associated with the common MT-ATP6 mutations. Of interest, four adult patients developed unexpected, subacute brainstem dysfunction akin to Leigh-like crisis, one patient had a stroke-like episode, and three patients exhibited symptoms similar to episodic ataxia. Conclusions and Relevance: The majority of patients with genetic defects of MT-ATP6 have cerebellar ataxia and peripheral neuropathy, and some degree of cognitive dysfunction seems relatively common among these patients. Moreover, some patients experience sudden exacerbations that are suggestive of a mitochondrial energy crisis and mandate active supportive treatment. These findings may be useful in the diagnostics and care of patients with MT-ATP6 related mitochondrial disease. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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