Mitochondrial disease criteria

TLDR

A consensus mitochondrial disease scoring system was developed to aid diagnosis in patients with suspected mitochondrial disorders. The study assessed the specificity of this scoring system in 61 children with suspected oxidative phosphorylation disorders confirmed by genetic mutation. Data from 44 genetically confirmed oxidative phosphorylation disorder patients were compared to 17 patients with nonmitochondrial multisystem disorders, all of whom had muscle biopsies. The scoring system achieved high specificity, with all oxidative phosphorylation disorder patients scoring above 6 and 73% above 8, while none of the nonmitochondrial disorder patients reached comparable scores, indicating its effectiveness and potential use before biopsy.

Abstract

<b>Background: </b> Based on a previous prospective clinical and biochemical study, a consensus mitochondrial disease scoring system was established to facilitate the diagnosis in patients with a suspected mitochondrial disorder. <b>Objective: </b> To evaluate the specificity of the diagnostic system, we applied the mitochondrial disease score in 61 children with a multisystem disease and a suspected oxidative phosphorylation disorder who underwent a muscle biopsy and were consecutively diagnosed with a genetic mutation. <b>Methods: </b> We evaluated data of 44 children diagnosed with a disorder in oxidative phosphorylation, carrying a mutation in the mitochondrial or nuclear DNA. We compared them with 17 children who, based on the clinical and metabolic features, also had a muscle biopsy but were finally diagnosed with a nonmitochondrial multisystem disorder by further genetic analysis. <b>Results: </b> All children with a genetically established diagnosis of a primary oxidative phosphorylation disorder had a mitochondrial disease score above 6 (probable mitochondrial disorder), and 73% of the children had a score above 8 (definite mitochondrial disorder) at evaluation of the muscle biopsy. In the nonmitochondrial multisystem disorder group, the score was significantly lower, and no patients reached a score comparable with a definite respiratory chain disorder. <b>Conclusions: </b> The mitochondrial disease criteria system has a high specificity to distinguish between mitochondrial and other multisystem disorders. The method could also be applied in children with a suspected mitochondrial disorder, prior to performing a muscle biopsy.