Saneto, Russel P.
Mayo Clinic
Division of Pediatric Neurology, Departments of Neurology and
Citations 2
The clinical utility of functional testing in fibroblasts to diagnose primary mitochondrial disease
Hove, Johan L.K. Van , Friederich, Marisa W. , Hove, Roxanne A. Van , Lee, Jessica C. , Knight, Kaz M. , Donovan, Tonia E, Silveira, Lori, Hirano, Michio, Abdenur, José E. , Cassiman, David, Cohen, Bruce H. , Elsea, Sarah H. , Enns, Gregory M., Gahl, William A, Gavrilova, Ralitza, Geddes, Gabriella C, Glamuzima, Emma E, Goldstein, Amy , Haas, Richard , Khan, Aneal , Kripps, Kimberly A. , Lehman, April, Lichter-Konecki, Uta, Morava, Eva, Rosenfeld, Jill A, Saneto, Russel P., Scaglia, Fernando , Shelkowitz, Emily , Smith, Wendy E, Soler-Alfonso, Claudia, Coster, Rudy N.A. Van, Vockley, Gerard, Wigby, Kristen, Wolfe, Lynne A. , Wortmann, Saskia B. , Van Hove, Johan L K , Ganetzky, Rebecca D , Cohen, Bruce H , Elsea, Sarah , Khan, Aneal , Larson, Austin A , Lehman, April N , Mayr, Johannes A , Scaglia, Fernando , Simon, Mariella , Smet, Joél E G , Tarnopolsky, Mark , Wolfe, Lynne A , Wortmann, Saskia , Yang, Jennifer H , Donovan, Tonia E., Ganetzky, Rebecca , Hirano, Michio , Butler, Merlin G. , Cassiman, David , Enns, Gregory M. , Gahl, William A. , Glamuzina, Emma E , Larson, Austin , Lichter‐Konecki, Uta , Morava, Éva , Peterson, James T. , Rosenfeld, Jill A. , Saneto, Russell P. , Smith, Wendy E. , Soler‐Alfonso, Claudia , Tarnopolsky, Mark A. , Vanlander, Arnaud Vincent , Vermeersch, Pieter , Wigby, Kristen M. , Yang, Jennifer H.
No container title available | June 16, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Genome sequencing of the heterogeneous primary mitochondrial disorders (PMD) frequently reveals variants of uncertain significance that require functional tests for diagnosis, and does not identify variants in all patients. We analyzed mitochondrial enzyme assays, blue native polyacrylamide gel electrophoresis (BN-PAGE) with in-gel activity staining, complex I assembly blot, and select protein abundances in fibroblasts of a case series of 204 PMD patients divided into functional classes, in comparison to 51 controls and 53 differential diagnostic conditions. Overall, sensitivity and specificity for respiratory chain enzyme assays were 46% and 93% respectively, for BN-PAGE 40% and 98%, for complex I assembly assay 49% and 99%. The overall sensitivity of all tests was 76%, specificity 93%, with positive predictive value 96% and negative predictive value 67%. Categories with high sensitivity were isolated complex deficiencies, nuclear DNA-encoded mitochondrial protein synthesis defects, co-factor defects, and mitochondrial amino-acyl-tRNA synthetase conditions when aided by protein abundance. Mitochondrial DNA mutations and maintenance disorders showed poor sensitivities. Secondary dysfunctions were rare. A complete battery of functional tests showed strong diagnostic clinical utility in fibroblasts. One sentence summary A combination of four mitochondrial functional tests to identify or confirm suspected primary mitochondrial disease in fibroblasts had good sensitivity and excellent specificity, well beyond what was perceived using enzyme assays only.
Neuroimaging of Early Life Epilepsy
Coryell, Jason , Gaillard, William D. , Shellhaas, Renée A. , Wusthoff, Courtney J. , Keator, Cynthia, Sullivan, Joseph , Loddenkemper, Tobias , Chu, Catherine J. , Massey, Shavonne L. , Saneto, Russel P., Berg, Anne T. , Wirrell, Elaine C., Shellhaas, Renée A , Gaillard, William D , Loddenkemper, Tobias , Berg, Anne T , Chu, Catherine J , Coryell, Jason , Wusthoff, Courtney J , Grinspan, Zachary M. , Wirrell, Elaine , Knupp, Kelly G. , Patel, Anup D. , Novotny, Edward J.
Pediatrics | August 8, 2018 | Volume: 142 | Issue: 3 | Pages: No page available
OBJECTIVES: We assessed the adherence to neuroimaging guidelines and the diagnostically relevant yield of neuroimaging in newly presenting early life epilepsy (ELE). METHODS: There were 775 children with a new diagnosis of epilepsy (<3 years old at onset) who were recruited through the ELE study at 17 US pediatric epilepsy centers (2012–2015) and managed prospectively for 1 year. The data were analyzed to assess the proportion of children who underwent neuroimaging, the type of neuroimaging, and abnormalities. RESULTS: Of 725 children (93.5%) with neuroimaging, 714 had an MRI (87% with seizure protocols) and 11 had computed tomography or ultrasound only. Etiologically relevant abnormalities were present in 290 individuals (40%) and included: an acquired injury in 97 (13.4%), malformations of cortical development in 56 (7.7%), and other diffuse disorders of brain development in 51 (7.0%). Neuroimaging was abnormal in 160 of 262 (61%) children with abnormal development at diagnosis versus 113 of 463 (24%) children with typical development. Neuroimaging abnormalities were most common in association with focal seizure semiology (40%), spasms (47%), or unclear semiology (42%). In children without spasms or focal semiology with typical development, 29 of 185 (16%) had imaging abnormalities. Pathogenic genetic variants were identified in 53 of 121 (44%) children with abnormal neuroimaging in whom genetic testing was performed. CONCLUSIONS: Structural abnormalities occur commonly in ELE, and adherence to neuroimaging guidelines is high at US pediatric epilepsy centers. These data support the universal adoption of imaging guidelines because the yield is substantially high, even in the lowest risk group.