Abstract
Mitochondrial diseases are usually severe and progressive conditions; however, there are rare forms that show remarkable spontaneous recoveries. Two homoplasmic mitochondrial tRNA mutations (m.14674T>C/G in mt-tRNAGlu) have been reported to cause severe infantile mitochondrial myopathy in the first months of life. If these patients survive the first year of life by extensive life-sustaining measures they usually recover and develop normally. Another mitochondrial disease due to deficiency of the 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) causes severe liver failure in infancy, but similar to the reversible mitochondrial myopathy, within the first year of life these infants may also recover completely. Partial recovery has been noted in some other rare forms of mitochondrial disease due to deficiency of mitochondrial tRNA synthetases and mitochondrial tRNA modifying enzymes. Here we summarize the clinical presentation of these unique reversible mitochondrial diseases and discuss potential molecular mechanisms behind the reversibility. Understanding these mechanisms may provide the key to treatments of potential broader relevance in mitochondrial disease, where for the majority of the patients no effective treatment is currently available.
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Acknowledgments
RH was supported by the Medical Research Council (UK) (G1000848) and the European Research Council (309548).
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All procedures followed were in accordance with the ethical standards of the responsiblecommittee on human experimentation (NRES Committee Yorkshire & The Humber-LeedsBradford) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consentwas obtained from all patients from our centre for being included in the study. This article does not contain any studies with animalsubjects performed by the any of the authors.
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Communicated by: Shamima Rahman
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Supplementary Table 1
Laboratory and muscle biopsy results of patients with RIRCD (DOCX 27 kb)
Supplementary Table 2
Laboratory and biopsy results of patients with TRMU deficiency (DOCX 26 kb)
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Boczonadi, V., Bansagi, B. & Horvath, R. Reversible infantile mitochondrial diseases. J Inherit Metab Dis 38, 427–435 (2015). https://doi.org/10.1007/s10545-014-9784-6
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DOI: https://doi.org/10.1007/s10545-014-9784-6