Testing & Diagnosis for Mitochondrial Disease in Children

How are mitochondrial disorders diagnosed?

Because symptoms are so varied, affecting multiple organs in the body, diagnosing mitochondrial disease can be challenging. Sometimes other disorders not involving the mitochondria are mistakenly diagnosed as mitochondrial disease. The opposite is true as well: Sometimes individuals who truly have mitochondrial disease are diagnosed as having something else.

Many symptoms of mitochondrial disease—such as failure to thrive, short stature, poor stamina, developmental delay, seizures, poor muscle tone, vomiting, severe constipation or diarrhea—have a variety of other causes. Because of this, it’s usually not a single symptom but a combination of two, three or more different symptoms that leads clinicians to suspect mitochondrial disease.

Genetic testing is the most reliable way to diagnose and categorize a mitochondrial disorder. We may recommend genetic testing for your child (and sometimes for parents too) if any of these symptoms are present:

  • developmental delay with involvement of other organs
  • dardiomyopathy (disease of the heart muscle) or unexplained heart block, or impaired electrical signals in the heart
  • high levels of lactate in the blood or cerebrospinal fluid, when other symptoms are present
  • certain abnormal findings on brain imaging
  • ophthalmoplegia (impaired eye movement) or ptosis (drooping upper eyelid)
  • hearing loss
  • severe gastrointestinal dysmotility (weak or lost muscular contractions in the intestines) or intestinal pseudo–obstruction (bowel obstruction caused by inability of the intestine to push food through)
  • significant developmental regression in the setting of an illness

Genetic testing often begins with analyzing the mitochondrial DNA and, if results are negative, testing the nuclear DNA for genes known to be involved in mitochondrial disease. If these tests come up negative, the child’s nuclear DNA may need to be completely analyzed through whole exome sequencing (this is similar to whole genome sequencing, but analyzes just the genes that code for proteins).

The type and depth of genetic testing we recommend will depend on the child’s symptoms and how strongly we suspect mitochondrial disease. Unfortunately, at this writing, extensive genetic testing is not always covered by insurance. If you or your child is in need of testing, we will work with your insurance companies to help with the process of approval.

Additional, non-genetic tests also help in diagnosing mitochondrial disorders. They include:

  • biochemical tests on urine, blood and spinal fluid
  • a muscle biopsy to examine the mitochondria and test enzyme levels
  • magnetic resonance imaging (MRI) of the brain and spine

If a mitochondrial disorder is suspected or identified, we may refer your child for further testing and consultations with specialists. Testing depends on symptoms, and may include:

  • echocardiography
  • electrocardiography (EKG)
  • eye examinations
  • hearing tests