Mitochondrial Disease | Diagnosis & Treatment

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:

Managing your child's condition

While mitochondrial disorders have no cure, children often do better when symptoms are caught and addressed early. Your child will be followed closely and screened for a variety of conditions related to mitochondrial disease, such as heart, vision and hearing problems. Symptoms can often be alleviated by maintaining good general health, including careful attention to nutrition and avoiding infections and dehydration.  

Exercise is one of the few proven methods for improving mitochondrial functioning and can help preserve your child’s strength and endurance. Exercise regimens should be supervised, should build up very gradually in intensity and should be suspended during illness.

What are the treatment options for mitochondrial disorders?

Currently, vitamins and supplements are the mainstay of treatment for mitochondrial disorders. They are thought to help mitochondria produce energy and reduce accumulation of toxic compounds inside cells. These supplements and cofactors are sometimes given together in “cocktails.” At present, the compounds that have been most well tested include coenzyme Q10 and creatine, but we also use a great variety of other supplements.

Regimens for specific mitochondrial disorders may include compounds that are deficient because of the disease, such as arginine (in MELAS) and folinic acid (in Kearns-Sayre syndrome). At Boston Children’s, we are testing dichloroacetate (DCA), which counters the high levels of lactic acid found in some mitochondrial disorders. In certain disorders, we may prescribe a special diet.

Supportive care

Because children with mitochondrial disease tend to be very sensitive to the stresses caused by minor illnesses like colds and fevers, your clinician will sometimes prescribe additional supportive therapies when the child is sick. These can include vitamins, cofactors, medications to counter biochemical imbalances that may occur, beverages containing electrolytes and sometimes intravenous (IV) hydration and IV antibiotics. In some instances, your child may need to be monitored in the hospital.

Children with mitochondrial disease also are known to be sensitive to a variety of drugs, as well as anesthetics used for surgical procedures.