Simplified testing for a challenging diagnosis    

Advanced genetic analysis for successful diagnosis

The symptoms and age of onset of mitochondrial syndromes can vary substantially. From atypical symptom presentation in even well-described, classic mitochondrial syndromes, to differing presentations among members of the same family, disease presentation is highly variable.

Mutations in mitochondrial DNA are maternally inherited. However, each cell contains many mitochondria — some with and some without the mutation — that might result in localized symptoms and varying severity at age of onset. Mutations in nuclear DNA can be inherited through an autosomal dominant, autosomal recessive, or X-linked manner. Standard biochemical workups frequently demonstrate some normal and some abnormal results. Additionally, different specimen types may yield different results for the same analysis.

A streamlined approach

The complexity of mitochondrial disease and the amount of clinical and lab data collected on each patient requires expertise to integrate and understand. Our laboratory directors work closely with genetic counselors, neurologists, and medical geneticists to bring a wealth of knowledge and experience in both laboratory and clinical practice to the test development arena. Our genetic counselors are available to support test selection and interpretation, ensuring the most appropriate test for each patient.

Mayo Clinic Laboratories offers four molecular test options that can complement radiological and histological evaluations to confirm a mitochondrial diagnosis and identify a specific mitochondrial syndrome. Rather than a series of targeted panels or single-gene analysis, our recommended approach is sequencing the entire mitochondrial genome and/or performing a comprehensive nuclear gene panel.

Pioneering technology provides precision results

Our innovative testing employs droplet digital polymerase chain reaction (ddPCR) technology, which is the most sensitive method on the market for detecting mitochondrial DNA deletions and duplications. This highly sensitive test is the only available method that enables achievement of absolute, rather than relative/indirect, quantification of heteroplasmy, which significantly reduces the risk of false negative and false positive results.

Mayo Clinic Laboratories’ assay also uses six different primer sets to successfully capture copy number variants that fall outside of normal breakpoints typically detected by other laboratory tests. This testing approach has enabled successful diagnoses in patients who have previously received false positive or false negative results through testing performed at other laboratories.

GDF15: A novel biomarker for mitochondrial disease

Growth differentiation factor 15 (GDF15) has been shown by studies on mitochondrial disease patients to be significantly elevated in plasma or serum. Based on our experience and review of recent publications, GDF15 demonstrates high sensitivity for mitochondrial disease — with the exception of patients with neuropathy, ataxia, and retinitis pigmentosa (NARP), pyruvate dehydrogenase deficiency, and a small subset of MELAS patients. High elevations of GDF15 appear to have a useful role, alongside other mitochondrial disease biomarkers, such as blood lactate, in the evaluation of patients with suspected mitochondrial disorders.

When to consider testing

According to the National Institutes of Health, the following red flag warnings1 should immediately increase the suspicion of a mitochondrial disorder:

  • Short stature
  • Neurosensory hearing loss
  • Progressive external ophthalmoplegia
  • Axonal neuropathy
  • Diabetes mellitus
  • Hypertrophic cardiomyopathy
  • Renal tubular acidosis 

Molecular testing

Confirming a mitochondrial diagnosis or identifying a specific mitochondrial syndrome requires molecular testing. Mayo Clinic Laboratories offers test options to analyze either the mitochondrial genome, a comprehensive panel of nuclear genes involved in mitochondrial disease, or both. For a complete list of genes included in our sequencing panels, please visit our online test catalog.

Biochemical testing

The diagnostic process for mitochondrial disease may begin with a set of biochemical tests that, when abnormal, can be indicative of a metabolic disorder. Correlating biochemical laboratory results with the clinical presentation and other test results can further confirm suspicion of mitochondrial disease. Mayo Clinic Laboratories offers a comprehensive menu of biochemical genetic tests that can help detect mitochondrial disorders. They include:

Test in Focus

Linda Hasadsri, M.D., Ph.D., discusses Mayo Clinic Laboratories’ comprehensive approach to testing for mitochondrial disease, which can be a diagnostic challenge because of the highly variable clinical presentation. Our full suite of biochemical and molecular assays uses custom-designed sequencing reagents that enable greater coverage of genomic areas of interest. These assays focus on detecting biomarker and genetic variations to diagnose this elusive, multisystem condition.

Learn more about how to order these tests at your institution.


  1. Koenig MK. Presentation and diagnosis of mitochondrial disorders in children. Pediatr Neurol. 2008;38(5):305-313. doi:10.1016/j.pediatrneurol.2007.12.001.