医疗专业人员

June 25, 2019

Mayo Clinic uses comprehensive next-generation sequencing panels for the diagnosis of neurogenetic disorders, including neuropathy, epilepsy and neuromuscular conditions. The testing covers the expanding genotype-phenotype complexity of these conditions, facilitating timely, accurate diagnosis and optimal treatment.

"Many patients with these disorders keep circling back — getting additional referrals and repeating the same tests without getting an answer. We have developed targeted panels in an effort to provide quicker diagnosis of genetic causes and cost benefits," says Christopher J. Klein, M.D., a neurologist at Mayo Clinic in Rochester, Minnesota. "We are committed to developing tests that provide accuracy and value."

The epilepsy and neuromuscular testing allows physicians to order custom gene panels. "Occasionally a physician might have a patient whose phenotype runs so true to the disorder that testing for the whole panel isn't needed — only a couple of genes," Dr. Klein says. At Mayo Clinic Laboratories, physicians can select the genes they wish to have tested; the genes listed on the lab's website link to an online catalog of human genes and genetic disorders, for additional information.

Algorithms to guide diagnosis

Mayo Clinic has developed and published diagnostic algorithms that utilize the targeted next-generation sequencing approach as well as onset age, family history and bedside clinical findings. The algorithms are clickable PDFs with links to the recommended testing.

The hereditary peripheral neuropathy algorithm includes a neuropathy test panel that incorporates 197 genes. Identifying a genetic cause for neuropathy has significant therapeutic implications. For example, last year the Food and Drug Administration approved two medications for the treatment of transthyretin (TTR) amyloidosis, a severe form of inherited neuropathy.

"If TTR amyloidosis is caught early, these drugs can reverse it. If the diagnosis is made later, the drugs can stop the neuropathy from progressing," Dr. Klein says. "That's the future of neurogenetics — finding therapies that target particular genes." He notes that laboratory research is underway to find additional therapies targeting PMP22, another gene associated with the most commonly known inherited neuropathy.

Similar testing algorithms for familial epilepsy and inherited neuromuscular myopathy are available from Mayo Clinic Laboratories. They were developed under the leadership of Erik C. Thorland, Ph.D., and Zhiyv (Neal) Niu, Ph.D. As with inherited neuropathy, the goal for familial epilepsy and neuromuscular myopathy is timely diagnosis and treatment.

"Genetic epilepsy often presents in infants with devastating consequences," Dr. Klein says. "Finding a genetic abnormality can sometimes lead to a change in medical management." Mayo Clinic's unexplained refractory and/or familiar epilepsy algorithm also includes metabolic tests and autoimmune evaluations that might be considered.

Identifying a genetic cause for a neuromuscular condition can sometimes help a patient avoid a muscle biopsy. "There remains a role for biopsies, if the test panel results are negative or inconclusive," Dr. Klein says. "But at Mayo Clinic, we are working to reduce unnecessary and invasive tests."

New test for NAM

In addition to neurogenetic panels, Mayo Clinic has a range of autoimmune neurology testing ― including a new test for necrotizing autoimmune myopathy (NAM), a serious muscle disease. A rare subset of people with NAM have a chronic disease course that can be mistaken for genetic forms of the disease. Early, aggressive immune therapy management can improve outcomes for people with NAM.

Mayo Clinic's test is a single evaluation that incorporates both antibodies commonly associated with NAM — HMGCR-IgG and SRP-IgG. The detection of SRP-IgG is facilitated by a highly sensitive immunofluorescence-based assay that can discern the distinctive, characteristic pattern in a patient's serum.

"At Mayo Clinic, we talk about matching the right patient with the right doctor," Dr. Klein says. "Similarly, we are trying to match the right patient with the right test, for the greatest value and most rapid and accurate diagnosis."

For more information

Custom gene ordering. Mayo Clinic Laboratories.

Hereditary Peripheral Neuropathies Diagnostic Algorithm. Mayo Clinic Laboratories.