While some people have specific and textbook-like symptoms of a distinct syndrome such as Leber hereditary optic neuropathy (LHON), many individuals with mitochondrial disease have a variety of symptoms involving multiple body systems or organs. Common symptoms can include generalized development disability, features of autism spectrum disorder, intellectual disabilities, muscle weakness, seizures, peripheral neuropathy, cardiomyopathy, liver and kidney disease, vision loss (ophthalmoplegia, retinitis pigmentosa), hearing loss, and diabetes mellitus.

It is estimated that 250-300 genes comprise or regulate the function of the respiratory chain complex, the majority of which are genes that reside in the cell’s nucleus, not the mitochondria.  In fact, 80-90% of mitochondrial disorders are caused by nuclear DNA (nDNA) variants. However, the remaining 10-20% are caused by variants in the 37 genes coded by DNA that resides in the mitochondria (mtDNA). This mitochondrial DNA is separate from the nuclear DNA and needs to be tested separately. Unlike nuclear DNA which is inherited from both parents, mitochondrial DNA is only inherited from the mother. 

NextStep^Dx PLUS® will analyze the nuclear DNA for genetic variants while mitochondrial DNA testing will analyze the mitochondrial DNA. Ordering both tests maximizes the chance of identifying a cause for an individual’s clinical features. These tests can be done on a single cheek swab and are reported together by the same clinical team for the most comprehensive assessment.

Mitochondrial DNA results are often complex and challenging to interpret due to a phenomenon known as heteroplasmy. This means that a cell has many mitochondria and therefore, has multiple copies of mitochondrial DNA. Within this cell, the copies of mitochondrial DNA may be different from each other, meaning some mitochondrial DNA will have genetic variants while others do not. This mixture is called heteroplasmy. The percentage of heteroplasmy and type of tissue with heteroplasmy often predicts whether a person will have symptoms and what those symptoms may be.  In general, the higher the percentage of heteroplasmy, the more severe the symptoms.

We estimate the turnaround time to be 8 to 12 weeks.