Treatable mitochondrial diseases: cofactor metabolism and beyond

Sir, In the past, numerous articles related to disorders of mitochondrial cofactor metabolism have been published in Brain (Ozand et al. , 1998; Gempel et al. , 2007; Johnson et al. , 2012; Foley et al. , 2014; Haack et al. , 2014; Ortigoza-Escobar et al. , 2016). These studies not only facilitated our understanding of the underlying biochemical defects, but also paved the way to specific treatment options. As a consequence our clinical view on mitochondrial diseases has changed substantially during the last years. The umbrella term ‘mitochondrial disease’ comprises a large group of inherited metabolic disorders caused by dysfunction of the pyruvate oxidation route. Our common understanding of mitochondrial diseases mainly refers to classical mitochondrial syndromes such as Leigh syndrome or MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). However, the spectrum of mitochondrial diseases is much broader and the development of novel genetic tools has undeniably advanced our knowledge about this disease group. During the past 6 years more than 100 novel mitochondrial diseases have been identified via next generation sequencing (NGS) strategies leading to a total number of around 280 known disease genes, affecting diverse mitochondrial pathways. Accordingly, clinical management of affected individuals is challenging and diagnostic strategies are in flux. Unfortunately, current therapeutic options for the majority of classical mitochondrial syndromes are limited to supportive care. Nevertheless, apart from these prognostically unfavourable diseases, there are several mitochondrial defects that are amendable by specific treatment strategies (Table 1). Among the group of these ‘treatable mitochondrial diseases’, defects of cofactor metabolism play a major role. View this table: Table 1 Inherited mitochondrial diseases with specific treatment options For …