Primary mitochondrial disorders

Last revised by Dr Jeremy Jones on 31 Jan 2021

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: 

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 dependent 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 dependent 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:

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Cases and figures

  • Case 1: Leigh disease
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  • Case 2: MELAS
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  • Case 3: POLG1 mutation
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