Primary mitochondrial disorders
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At the time the article was created Frank Gaillard had no recorded disclosures.View Frank Gaillard's current disclosures
At the time the article was last revised Ashesh Ishwarlal Ranchod had no financial relationships to ineligible companies to disclose.View Ashesh Ishwarlal Ranchod's current disclosures
Primary mitochondrial disorders (PMDs) are a clinically heterogeneous group of conditions caused by pathologic variants in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA).
There are many conditions that result from mitochondrial dysfunction affect the neurological and muscular systems in a variety of ways:
- Kearns-Sayre syndrome
- Leigh syndrome
- MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes)
- MERRF (myoclonus epilepsy with ragged red fibers)
- mitochondrial deletion syndromes, e.g. POLG-related disorders
- trichopoliodystrophy (also known as Menkes disease)
Primary mitochondrial disorders are clinically (and radiologically) heterogeneous. They may occur at any age and can manifest with a broad range and severity of symptoms. The disorders may affect any system, but tissues that are highly dependant on aerobic metabolism and have high energy requirements are usually those that are affected. Thus, in many of these disorders, the CNS, heart and skeletal muscle are disproportionately affected.
Primary mitochondrial disorders occur when variation in the mitochondrial (mtDNA) or nuclear (nDNA) DNA results in pathological abnormality. The genes located in mitochondrial DNA demonstrate a degree of heterogeneity within the one individual: not all mitochondria share the same genetic material. The percentage of affected mitochondria will dictate the degree to which the disease is clinically manifested 1. As spermatozoa are deficient of mitochondria, these diseases are only inherited from the mother.
Findings in primary mitochondrial disorders are variable because the imaging findings are dependant on which organs and tissues are affected and how severe they are affected.
Imaging findings in these conditions may vary from patient to patient. They may be normal, specific for the disease, or non-specific 5. Often, there is a progression over time.
As a general rule of thumb bilateral deep grey matter involvement and peripheral white matter delayed myelination in young adults or children should suggest the diagnosis. This is especially the case if associated with an elevated lactate level on MRS.
Common CNS primary mitochondrial disorders that present with a typical imaging phenotype include:
- 1. Barkovich AJ, Good WV, Koch TK et-al. Mitochondrial disorders: analysis of their clinical and imaging characteristics. AJNR Am J Neuroradiol. 14 (5): 1119-37. AJNR Am J Neuroradiol (abstract) - Pubmed citation
- 2. Koga SJ, Hodges M, Markin C et-al. MELAS syndrome. West. J. Med. 1995;163 (4): 379-81. - Free text at pubmed - Pubmed citation
- 3. Cheon JE, Kim IO, Hwang YS et-al. Leukodystrophy in children: a pictorial review of MR imaging features. Radiographics. 2002;22 (3): 461-76. doi:10.1148/radiographics.22.3.g02ma01461 - Pubmed citation
- 4. DiMauro S, Hirano M. Mitochondrial DNA Deletion Syndromes. 2003 Dec 17 [Updated 2011 May 3]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1203/
- 5. Saneto RP, Friedman SD, Shaw DW. Neuroimaging of mitochondrial disease. Mitochondrion. 8 (5-6): 396-413. doi:10.1016/j.mito.2008.05.003 - Pubmed