Primary genetic mitochondrial diseases are often difficult to diagnose, and the term ‘possible’ mitochondrial disease is used frequently by clinicians when such a diagnosis is suspected. There are now many known phenocopies of mitochondrial disease. Advances in genomic testing have shown that some patients with a clinical phenotype and biochemical abnormalities suggesting mitochondrial disease may have other genetic disorders. In instances when a genetic diagnosis cannot be confirmed, a diagnosis of ‘possible’ mitochondrial disease may result in harm to patients and their families, creating anxiety, delaying appropriate diagnosis and leading to inappropriate management or care. A categorisation of ‘diagnosis uncertain’, together with a specific description of the metabolic or genetic abnormalities identified, is preferred when a mitochondrial disease cannot be genetically confirmed.
- metabolic disorders
- clinical genetics
- evidence based practice
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SP and AK contributed equally.
Contributors SP, AK and AG conceived the presented idea and prepared a document outline including needed supplementary material. SP, AK, AG and SR developed and supervised the manuscript. SP, AK, AG, ESB, PFC, JC, BHC, RLD, MJF, CF, RH, MKK, MM, SM, EMM, RM, VN, MS, HS, SS, CS, MT, DRT, JV and SR commented on, approved and helped expand on the presented idea, drafted and revised portions of the manuscript including supplementary materials and commented on and approved the final draft.
Funding RH is a Wellcome Trust Investigator (109915/Z/15/Z), who receives support from the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z), Medical Research Council (UK) (MR/N025431/1), the European Research Council (309548), the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z) and the Newton Fund (UK/Turkey, MR/N027302/1). PFC is a Wellcome Trust Senior Fellow in Clinical Science (101876/Z/13/Z) and a UK NIHR Senior Investigator, who receives support from the Medical Research Council Mitochondrial Biology Unit (MC_UP_1501/2), the Medical Research Council (UK) Centre for Translational Muscle Disease (G0601943), EU FP7 TIRCON and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. SR is supported by a Great Ormond Street Hospital Children’s Charity Research Leadership Award (V1260) and by research grant funding from the NIHR Great Ormond Street Hospital Biomedical Research Centre and the Lily Foundation. ESB, SR and MR are members of the European Reference Network for Rare Hereditary Metabolic Disorders (METABERN)—Project ID No 739543. MetabERN is partly cofunded by the European Union in the framework of the Third Health Programme ‘ERN-2016—Framework Partnership Agreement 2017-2021’. MM is supported by research grants from Telethon and MITOCON Italian patients’ association (grants GSP09004 and GSP16001).
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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