[1507] 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), 
4
m 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 mean
SD.
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.
| AURC | Cutoff | P-value | Sensitivity | Specificity | |
| 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 |
| SSMA (%) | 0.54 | >28.3 | 0.71 | 22.2 | 100.0 |
Conclusions: Because of improved specificity, a LSSMA >3.3% should be considered as a potential major criterion for diagnosis of mitochondriopathy in children.
Category: Neuropathology
Monday, March 9, 2009 1:00 PM
Platform Session: Section H, Monday Afternoon