What is the role of lab tests in the workup of Charcot-Marie-Tooth (CMT) disease?

Updated: Feb 19, 2019
  • Author: Francisco de Assis Aquino Gondim, MD, PhD, MSc, FAAN; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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When considering an inherited neuropathy, the goal is to prove or refute this diagnosis and possibly discover coexisting treatable condition such as nerve entrapment and acquired neuropathy. Thus, the workup must address causes of neuropathies such as endocrine, infectious, immunologic, vitamin and nutritional abnormalities, deficiencies, and nerve compression. Required screening tests include rapid plasma reagin, vitamin B-12, folate, antinuclear antibodies, erythrocyte sedimentation rate, thyroid-stimulating hormone (TSH), and serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP).

Recognize that standard SPEP is too insensitive to identify small quantities of monoclonal proteins that may well be pathogenic, and it must routinely be replaced by serum immunofixation electrophoreses (IFE). Similarly, clinically relevant vitamin B-12 deficiency is not excluded by a reference range vitamin B-12 level equal to or above 170 ng/L (111 pM/L) for the radioimmunoassay and 250 ng/L (184 pM/L) for the chemiluminescent assay. When suspected, this test must be supplemented by methylmalonic acid and homocysteine levels.

Findings on cerebrospinal fluid (CSF) analysis are usually normal in CMT, but protein is often high in DSS; protein was high in a patient with PMP22 deletion and recurrent polyradiculoneuropathy.

Perform pedigree analysis. Establishing inheritance patterns, if available, can narrow the differential diagnosis and eliminate the need for some genetic tests. For instance, CMT1X becomes unlikely with well-documented male-to-male transmission.

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