Quantitation of Large Subsarcolemmal Mitochondrial Aggregates Improves Specificity for Diagnosis of Mitochondriopathy in Children
L Miles, KE Bove, PS Horn, MV Miles. Children's Healthcare of Atlanta, Atlanta, GA; Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Background: In the diagnosis of mitochondriopathy the presence of ragged red fibers and COX-negative fibers is helpful, but these features are uncommon in muscle biopsies from children. Until recently >2% of myofibers containing subsarcolemmal mitochondrial aggregates (SSMA) was proposed as a minor criterion for diagnosis of mitochondriopathy. The current authors suggested previously that only large SSMA (LSSMA), 4m in thickness, are useful for the diagnosis of mitochondriopathy. The current study compares the sensitivity and specificity of % of myofibers containing LSSMA, SSMA, type 1 myofiber, and for each patient, the lowest individual electron transport chain (ETC) complex activity in the diagnosis of mitochondriopathy.
Design: Only patients with previously identified LSSMA and ETC testing in muscle were included in this study. The discriminative performances of LSSMA(%), SSMA(%), type I myofiber predominance(%), and lowest individual ETC complex activity (% of mean control) result were evaluated for the diagnosis of mitochondriopathy using receiver operating characteristic (ROC) analysis. Results are expressed as meanSD.
Results: In 35 patients with LSSMA, 9 [age 7.37.8y] had mitochondriopathy (group 1) and 26 [age 4.32.9y] had no evidence of mitochondriopathy (group 2). Group 1 patients had increased LSSMA (p=0.007) compared to group 2, 4.73.4% vs. 1.71.0%, respectively. Type I myofiber (%) and SSMA (%) were similar between groups. ETC complex activities were similar except for decreased complex I+III activity in group 1 (p=0.008). ROC analysis results are summarized in the table. Logistic regression modeling indicated that the diagnostic performance was significantly improved (Area Under the ROC Curve=0.938) with the combined use of LSSMA and ETC testing.
Comparison of ROC ResultsAURC; area under ROC curve
|Lowest ETC activity (%)||0.80||40.0||0.0001||77.8||88.5|
|Large SSMA (%)||0.81||>3.3||0.0013||66.7||96.2|
|Type I Myofiber (%)||0.59||>60.0||0.44||55.6||68.0|
Conclusions: Because of improved specificity, a LSSMA >3.3% should be considered as a potential major criterion for diagnosis of mitochondriopathy in children.
Monday, March 9, 2009 1:00 PM
Platform Session: Section H, Monday Afternoon