Participants who had not been genetically tested for DM2 were included if they met the following criteria: 1) clinically suspected DM2; 2) medical council weakness of 4 or fewer at an upper or lower extremity; 3) electrodiagnostic or clinical myotonia (as demonstrated through grip contraction, percussion of the wrist extensors, or percussion of the thenar eminence region); and, 4) negative genetic testing for DM1 or negative genetic testing for DM1 in a similarly affected first degree relative.

All selected DM2 participants had previously received care at the University of Rochester in the Muscular Dystrophy Association (MDA) clinic, outpatient setting, electrodiagnostic laboratory, or through their participation in a University of Rochester DM2 clinical trial. Eighty-three DM2 patients were identified; 49 of which had recorded baseline laboratory data. Twenty-nine of these patients were male; 20 were female.

Each participant underwent multiple laboratory studies, although none underwent all 68 separate tests. Patients were divided into male and female study groups. Laboratory reference ranges were defined based on standardized test reference ranges from the University of Rochester Medical Center Clinical Laboratories on April 5, 2010. These ranges are set through varied methods, including local volunteer testing and outside data accumulation. Where ever applicable, sex specific ranges were defined. In instances in which standard laboratory ranges were based on menstrual staging (i.e., levels of follicle-stimulating hormone (FSH) and luteinizing hormone) the reference range was broadened to include all possible premenstrual and postmenopausal values. Sex specific reference ranges were utilized to determine whether a laboratory value was high, low, or normal.

All together, 10 laboratory tests from Table 1 had abnormal values in more than 40% of DM2 patients tested. These tests included the levels of creatine kinase (CK), IgG, total cholesterol, lactate dehydrogenase (LD), alanine aminotransferase (ALT), creatinine, serum glucose, total protein, and the absolute lymphocyte and absolute basophil counts. For some studies, the DM2 values were consistently high (i.e., CK, total cholesterol, and ALT levels), whereas other studies demonstrated frequent low values (i.e., IgG, creatinine, and total protein levels). Still other studies had both abnormally high and low values (i.e., serum glucose level).

Certain laboratory tests showed no abnormalities. These included potassium, sodium, total bilirubin and IgA.

The tabulated data add to previous clinical reports of abnormal laboratory values in DM2. Before this study, the two most commonly reported DM2 laboratory values were creatine kinase and gamma-glutamyltransferase (GGT). In one of the initial clinical descriptions of DM2 (then called proximal myotonic myopathy), 18 of 26 patients [69%] had elevated creatine kinase levels and 14 of 18 patients [78%] had higher GGT levels then their stated reference range.(6) Similarly, Day et al observed that 90% of DM2 patients had elevated CK levels, and 64% had elevated GGT levels. In a population of Italian and American families with DM2, Meola and Moxley reported that 60% of their patients had elevations in CK levels and 58% had increased GGT levels.(7) Although the present study demonstrated a similar elevation in CK levels (31 of 40 patients tested [78%]), only 33% of the patients had elevations in their GGT levels. Compared to a similarly studied myotonic dystrophy type-1 (DM1) population, on average, the present DM2 patients had higher CK levels (DM2: 537 u/L; DM1: 183 u/L) and lower GGT levels (DM2: 61.1 u/L; DM1: 110.4 u/L). (5)

In 2003, Day et al observed that 29% of patients with DM2 had low testosterone levels, 65% had high follicle-stimulation hormone levels, and 75% had insulin insensitivity (elevated basal insulin levels or prolonged insulin elevation).(3) Decreased levels of luteinizing hormone have also been reported.(8) Although endocrinologic laboratory sampling was limited in this study, we found similar trends in this population. Five of twelve patients had elevated follicle-stimulation hormone levels and one of eleven had a low level of luteinizing hormone. In seven patients who had their testosterone tested, one had a low level and three had values higher than the standard reference range. It is unknown, however, whether any of these patient were taking testosterone supplementation at the time of testing. Although none of the present patients had basal insulin level testing, 9 of 30 [30%] had baseline serum glucose elevations.

An association between autoimmune laboratory dysfunction and DM2 has been previously hypothesized.(9) Day et al reported that although DM2 patients have normal IgA levels, 65% have low IgG levels and 11% have low IgM levels.(3) Similarly, 17 of the present DM2 patients had normal IgA levels, 12 of 16 [75%] had low IgG levels, and 2 of 17 [12%] had low IgM levels. We also found that 5 of 14 [36%] had elevations in their IgE values.

This research provides a deeper glimpse into the widespread clinical manifestations of a relatively rare, recently discovered, and understudied dystrophy. These data may provide an identifiable disease/laboratory profile to assist in the initial identification of undiagnosed cases. Indeed there are clinical reports of DM2 patients being diagnosed presymptomatically secondary to the identification of elevated CK levels during routine blood work.(10) Similarly, the identification of other clinical markers such as elevated total cholesterol, lactate dehydrogenase and ALT levels, or reductions in IgG levels, lymphocyte counts, or creatinine levels may improve a physician’s ability to recognize an undiagnosed case of DM2.

These data also emphasizes the increased frequency of several potentially treatable conditions in the DM2 population. DM2 patients were found to have laboratory markers suggestive of hypercholesterolemia, hypertriglyceridemia, insulin insensitivity, and possibly malnutrition. The presence of such conditions, as manifested by high cholesterol levels, high triglyceride levels, high serum glucose levels, and low albumin and globulin levels may be amendable to early screening, pharmacologic therapeutics, or alterations in diet. The early identification of comorbid states in an at risk DM2 population has the potential to lead to early treatment and improved clinical outcomes for this population. DM2 patients had nearly identical mean albumin levels as their DM1 counterparts.(5) These albumin reductions may correspond to dysphagia, dietary habits, or impaired intestinal absorption in these two populations.(11) All three of these mechanisms may represent potential avenues for early clinical intervention for these two populations.

Similar to DM1, there was a high proportion of elevated liver enzyme levels (ALT, lactate dehydrogenase, GGT, and aspartate aminotransferase) in DM2. Although GGT elevations may suggests underlying hepatocyte involvement, it is possible that the ALT, lactate dehydrogenase, and aspartate aminotransferase abnormalities are, at least in part, due to underlying muscle abnormalities caused by DM2. In the present study no patient with an elevated aspartate aminotransferase or ALT level had a simultaneously normal CK level. In the past, patients have reported being sent for liver biopsies before being diagnosed as having DM2. Such hepatic biopsies generate extra risk, cost, and discomfort to DM2 patient without providing clear benefit. Through additional education regarding the DM2 phenotype and associated laboratory abnormalities it may be possible to limit future unnecessary referrals for hepatic biopsies. Knowledge of liver enzyme abnormalities may also assist physicians and researchers who serially follow DM2 patients. Baseline and periodic monitoring of liver enzyme levels should be considered before implementing any DM2 therapy. Without such testing, potentially helpful treatments could be discontinued secondary to the misperception of drug induced hepatic toxicity.

The results of this study may underestimate the degree and number of laboratory abnormalities in the DM2 community. A substantial portion of the patients included in this research were selected given their previous participation in controlled DM2 clinical trials. Because these clinical trials excluded patients with significant comorbidities it is possible that this dataset represents a “healthier” subset of DM2 patients. In addition, for DM2 participants who did not participate in a clinical trial, their earliest known laboratory studies were utilized when multiple values were available. By selecting these earlier tests results it is possible that these data underrepresented the progressive systemic dysfunction thought to occur as DM2 patients age.(3) Also note that co-existing medication use was not known during each individual laboratory sampling. It is possible that abnormal thyroid, testosterone, or lipid levels were masked by simultaneous drug use in a portion of patients studied.