RT Journal Article SR Electronic T1 High predictive value of brain MRI imaging in primary mitochondrial respiratory chain deficiency JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP jmedgenet-2017-105094 DO 10.1136/jmedgenet-2017-105094 A1 Isaure de Beaurepaire A1 David Grévent A1 Marlène Rio A1 Isabelle Desguerre A1 Pascale de Lonlay A1 Raphaël Levy A1 Volodia Dangouloff-Ros A1 Jean-Paul Bonnefont A1 Giulia Barcia A1 Benoit Funalot A1 Claude Besmond A1 Metodi D Metodiev A1 Benedetta Ruzzenente A1 Zahra Assouline A1 Arnold Munnich A1 Agnès Rötig A1 Nathalie Boddaert YR 2018 UL http://jmg.bmj.com/content/early/2018/01/21/jmedgenet-2017-105094.abstract AB Background Because the mitochondrial respiratory chain (RC) is ubiquitous, its deficiency can theoretically give rise to any symptom in any organ or tissue at any age with any mode of inheritance, owing to the twofold genetic origin of respiratory enzyme machinery, that is, nuclear and mitochondrial. Not all respiratory enzyme deficiencies are primary and secondary or artefactual deficiency is frequently observed, leading to a number of misleading conclusions and inappropriate investigations in clinical practice. This study is aimed at investigating the potential role of brain MRI in distinguishing primary RC deficiency from phenocopies and other aetiologies.Methods Starting from a large series of 189 patients (median age: 3.5 years (8 days–56 years), 58% males) showing signs of RC enzyme deficiency, for whom both brain MRIs and disease-causing mutations were available, we retrospectively studied the positive predictive value (PPV) and the positive likelihood ratio (LR+) of brain MRI imaging and its ability to discriminate between two groups: primary deficiency of the mitochondrial RC machinery and phenocopies.Results Detection of (1) brainstem hyperintensity with basal ganglia involvement (P≤0.001) and (2) lactate peak with either brainstem or basal ganglia hyperintensity was highly suggestive of primary RC deficiency (P≤0.01). Fourteen items had a PPV>95% and LR+ was greater than 9 for seven signs. Biallelic SLC19A3 mutations represented the main differential diagnosis. Non-significant differences between the two groups were found for cortical/subcortical atrophy, leucoencephalopathy and involvement of caudate nuclei, spinothalamic tract and corpus callosum.Conclusion Based on these results and owing to invasiveness of skeletal muscle biopsies and cost of high-throughput DNA sequencing, we suggest giving consideration to brain MRI imaging as a diagnostic marker and an informative investigation to be performed in patients showing signs of RC enzyme deficiency.