Redefining phenotypes associated with mitochondrial DNA single deletion.

TitleRedefining phenotypes associated with mitochondrial DNA single deletion.
Publication TypeJournal Article
Year of Publication2015
AuthorsMancuso, M, Orsucci, D, Angelini, C, Bertini, E, Carelli, V, Comi, GPietro, Donati, MAlice, Federico, A, Minetti, C, Moggio, M, Mongini, T, Santorelli, FMaria, Servidei, S, Tonin, P, Toscano, A, Bruno, C, Bello, L, Ienco, ECaldarazzo, Cardaioli, E, Catteruccia, M, Da Pozzo, P, Filosto, M, Lamperti, C, Moroni, I, Musumeci, O, Pegoraro, E, Ronchi, D, Sauchelli, D, Scarpelli, M, Sciacco, M, Valentino, MLucia, Vercelli, L, Zeviani, M, Siciliano, G
JournalJ Neurol
Volume262
Issue5
Pagination1301-9
Date Published2015 May
ISSN1432-1459
KeywordsAcyl-CoA Dehydrogenase, Long-Chain, Adult, Databases, Factual, DNA, Mitochondrial, Female, Gene Deletion, Humans, Kearns-Sayre Syndrome, Lipid Metabolism, Inborn Errors, Male, Middle Aged, Mitochondrial Diseases, Muscular Diseases, Ophthalmoplegia, Chronic Progressive External, Phenotype, Retrospective Studies, Young Adult
Abstract

Progressive external ophthalmoplegia (PEO), Kearns-Sayre syndrome (KSS) and Pearson syndrome are the three sporadic clinical syndromes classically associated with single large-scale deletions of mitochondrial DNA (mtDNA). PEO plus is a term frequently utilized in the clinical setting to identify patients with PEO and some degree of multisystem involvement, but a precise definition is not available. The purpose of the present study is to better define the clinical phenotypes associated with a single mtDNA deletion, by a retrospective study on a large cohort of 228 patients from the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases". In our database, single deletions account for about a third of all patients with mtDNA-related disease, more than previously recognized. We elaborated new criteria for the definition of PEO and "KSS spectrum" (a category of which classic KSS represents the most severe extreme). The criteria for "KSS spectrum" include the resulting multisystem clinical features associated with the KSS features, and which therefore can predict their presence or subsequent development. With the new criteria, we were able to classify nearly all our single-deletion patients: 64.5% PEO, 31.6% KSS spectrum (including classic KSS 6.6%) and 2.6% Pearson syndrome. The deletion length was greater in KSS spectrum than in PEO, whereas heteroplasmy was inversely related with age at onset. We believe that the new phenotype definitions implemented here may contribute to a more homogeneous patient categorization, which will be useful in future cohort studies of natural history and clinical trials.

DOI10.1007/s00415-015-7710-y
Alternate JournalJ. Neurol.
Citation Key10.1007/s00415-015-7710-y
PubMed ID25808502
Grant ListGUP09004 / / Telethon / Italy