Produção Nacional
Revisado por pares
Parsing the differences in affected with LHON: genetic versus environmental triggers of disease conversion
2015; Oxford University Press; Volume: 139; Issue: 3 Linguagem: Inglês
10.1093/brain/awv339
ISSN1460-2156
AutoresValério Carelli, Pio D’Adamo, Maria Lucia Valentino, Chiara La Morgia, Fred N. Ross‐Cisneros, Leonardo Caporali, Alessandra Maresca, Paola Loguercio Polosa, Piero Barboni, A. De Negri, Federico Sadun, Rustum Karanjia, Solange Rios Salomão, Adriana Berezovsky, Filipe Chicani, Milton Moraes, Milton Moraes Filho, Rubens Belfort, Alfredo A. Sadun,
Tópico(s)ATP Synthase and ATPases Research
ResumoSir, Leber’s hereditary optic neuropathy (LHON) is one of the best-studied mitochondrial diseases (for review see Carelli et al. , 2004; Yu-Wai-Mann et al. , 2011). Classically, there is a subacute loss of central vision that affects prevalently males, peaking in young adulthood. After a few months, optic atrophy becomes evident and the patient enters a chronic phase, in most cases characterized by stable blindness. Infrequently a partial recovery of visual acuity occurs. Exceptions have been reported. Concerning age of onset, childhood cases seem to represent a different version of LHON that often resembles dominant optic atrophy (Barboni et al. , 2006), whereas very late-onset cases have also been reported, widening the spectrum (Shah et al. , 2008; Yu-Wai-Man et al. , 2008; Giraudet et al. , 2011; Dimitriadis et al. , 2014). There is also a certain degree of heterogeneity in clinical expression, ranging from mild to severe cases, and the rates of spontaneous recovery of vision vary with mutation type (Carelli et al. , 2004, 2011; Yu-Wai-Mann et al. , 2011). A maternally inherited mitochondrial DNA (mtDNA) mutation is necessary but not sufficient to develop optic neuropathy. There are three common mtDNA mutations affecting complex I (i.e. m.11778G>A/MT-ND4, m.3460G>A/MT-ND1 and m.14484T>C/MT-ND6). Most cases remain as asymptomatic carriers, with males much more likely than females to undergo conversion to the affected state. Thus, male prevalence and incomplete penetrance remain areas of active investigation. Environmental factors have now been demonstrated as frequent triggers of the disease. The most common is tobacco smoke, in combination with or without alcohol consumption (Sadun et al. , 2003), as corroborated by Kirkman and colleagues (2009) with their large survey of LHON affected and unaffected mutation carriers. More rarely, exposure to toxins, various forms of smoke, or certain …
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