Primary mitochondrial disorders

There are numerous many conditions that result from mitochondrial disorders thatdysfunction 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 (MELAS)
• myoclonusMERRF (myoclonus epilepsy with ragged red fibres (MERRF)
• mitochondrial deletion syndromes, e.g. POLG-related disorders
• trichopoliodystrophy (also known as Menkes disease)

Clinical presentation

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.

Pathology

As spermatozoa are deficient of mitochondria, these diseases are only inherited fromPrimary mitochondrial disorders occur when variation in the mothermitochondrial (mtDNA) or nuclear (nDNA) DNA results in pathological abnormality. The genes are located in mitochondrial DNA (mtDNA) of which there isdemonstrate 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.

Radiographic features

TheFindings in primary mitochondrial disorders are variable because the imaging findings are variable rangingdependant on which organs and tissues are affected and how severe they are affected.

Imaging findings in these conditions may vary from specific findings (uncommon)patient to patient. They may be normal, specific for the disease, or non-specific abnormalities (most common) as well as normal appearing studies ⁵. Findings are discussed separately for each condition listed above but as  Often, there is a progression over time.

Neuroimaging features

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.