Mitochondrial Disorders

Genetic testing for mitochondrial disorders

Mitochondria perform many different functions in tissues throughout the body. Therefore, the clinical spectrum of mitochondrial disorders is diverse, and symptoms can range from fatigue and exercise intolerance to developmental delay, hearing loss, seizures, strokes, heart failure, diabetes and kidney failure.

Mitochondrial disorders may be undetected with nuclear gene sequencing alone. Combining nuclear and mitochondrial DNA testing is a powerful tool for patients with clearly genetic presentations for which nuclear DNA testing would otherwise be negative.

  • We have added the entire mitochondrial genome to 30 of our panels
  • The mitochondrial genome is also available as its own test for patients with findings indicating mitochondrial disease or with previous negative nuclear DNA sequencing results.
  • Any individual mtDNA genes or the entire mitochondrial genome can be added to any panel at no additional cost (see Customization of Diagnostic Panels).
  • Our high-quality mtDNA testing includes both sequencing and copy number variant analysis for all the 37 mtDNA genes.

Next-generation sequencing (NGS) methodologies have emerged as the new gold standard for mtDNA genome sequencing because they allow significantly improved reliability and sensitivity of mtDNA genome analyses for point mutations, low-level heteroplasmy, and deletions, thereby providing a single test to accurately diagnose mtDNA disorders.

The performance of Blueprint Genetics mtDNA Testing

Heteroplasmy detection capabilities

  • SNVs: 92.3% sensitivity at 5% heteroplasmy
  • Indels: >94% sensitivity at 5% heteroplasmy
  • Large 500bp – 5,000kb deletions: down to 10% (at 99% sensitivity)


  • Mean sequencing depth of 18,224x
  • 100% of base pairs covered at 1,000x

Clinical presentation

Mitochondria are responsible for creating more than 90% of the energy needed by cells, thus, mitochondrial disease is essentially a chronic loss of cellular energy, where a failure to meet cellular energy demand results in a clinical phenotype. Therefore, it is not surprising that the parts of the body, such as the skeletal muscles, heart and brain, requiring the greatest amounts of energy are the typically affected. Because mitochondria perform so many different functions in different tissues, the clinical spectrum of mitochondrial disease is diverse.

Mitochondrial dysfunction should be considered in the differential diagnosis of any progressive, multisystem disorder (three or more organs), both in children and in adults, as mitochondrial disorders may present at any age. Many individuals with a mutation of mtDNA display a cluster of clinical features that fall into a discrete clinical syndrome, such as the Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged-red fibers (MERRF), neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS). The prevalence of mitochondrial disease has proven difficult to establish, mainly due to the clinical and genetic heterogeneity. The minimum prevalence has been estimated at 1 in 5,000.

Sample types

At Blueprint Genetics, molecular genetic testing can be carried out on DNA extracted from blood, however, DNA extracted from the affected tissue might be a better option in rare cases, as some pathogenic mtDNA mutations are not always detectable in blood. In these rare cases, skeletal muscle or liver are preferred tissue sources for mtDNA genome sequencing when available, given their high mtDNA content, reliance on mitochondrial respiration, and the possibility that they may harbor a tissue specific mtDNA mutation that is simply not present in blood. In addition to genetic diagnostic testing, biochemical tests in affected tissues, such as muscle or liver, and other blood or urine based biochemical markers may be useful in identifying mitochondrial disease.

Please note that Blueprint Genetics does not currently accept tissue samples other than blood or saliva for DNA extraction.  We can, however, accept DNA extracted locally from muscle or liver.

Please see our Sample requirements page for accepted sample types before ordering.

The entire mitochondrial genome is included in the following panels for conditions where symptoms or findings may be caused by mtDNA mutations. The entire mitochondrial genome or individual mtDNA genes can also be added to any panel at no additional cost (see Customization of Diagnostic Panels)


Ear, Nose & Throat


Metabolic Disorders





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