CDE Detailed Report

Disease: Mitochondrial Disease
Sub-Domain: Laboratory Tests and Biospecimens/Biomarkers
CRF: Biomarkers in Mitochondrial Disease

Displaying 1 - 19 of 19
CDE ID CDE Name Variable Name Definition Short Description Additional Notes (Question Text) Permissible Values Description Data Type Disease Specific Instructions Disease Specific Reference Population Classification (e.g., Core) Version Number Version Date CRF Name (CRF Module / Guideline) Sub Domain Name Domain Name Size Input Restrictions Min Value Max Value Measurement Type External Id Loinc External Id Snomed External Id caDSR External Id CDISC
C19561 Biomarker platelet assessment type BiomarkPlatAssessTyp Type of biomarker(s) assessed from platelets (high OXPHOS) samples. Type of biomarker(s) assessed from platelets (high OXPHOS) samples. Which biomarker(s) were assessed from the specimen's platelets (high OXPHOS) sample? OXPHOS enzymology;High resolution respirometry;Coenzyme Q10;Peripheral type benzodiazerpine OXPHOS enzymology;High resolution respirometry;Coenzyme Q10;Peripheral type benzodiazerpine Alphanumeric Kramer, P.A., et al., A Review of the Mitochondrial and Glcolytic Metabolism in Human Platelets and Leukocytes: Implications for their Use as Bioenergetic Biomarkers. REdox Biol, 2014. 2: P. 206-210. Hroudova, J., et al., Mitochondrial Respiration in Blood Platelets of Depressive patients. Mitochondrion, 2013. 13(6): P. 795-800. Martini, C., ET AL., Peripheral Benzodiazepine Binding Sites in Platelets of Patients Affected by Mitochondrial Diseases and Large Scale Mitochondrial DNA Rearrangements. Mol Med, 2002. 8(12): P. 841-6. Adult;Pediatric Supplemental 1.00 2014-12-19 10:55:10.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19551 Biomarker blood plasma specimen assessment type BiomarkBloodPlasmaSpecAssesTyp Type of biomarker(s) assessed from blood serum/plasma samples. Type of biomarker(s) assessed from blood serum/plasma samples. Which biomarker(s) were assessed from the specimen's blood (serum/plasma) sample? Lactate;Pyruvate;lactate/pyruvate ratio;Leukocyte Coenzyme Q10;Amino acids(emphasis on alanine, alanine/lysine ratio, alanine/phenylalanine+lysine ratio, alanine/phenylalanine+lysine ratio, citrulline);Carnitine levels;CPK;Creatine;Free glutathione (fGSH);oxidized disulfide (GSSG);fGSH/GSSG ratio;Plasma carbonyl content;Fibroblast growth factor 21 (fgf21);Metabolic profiling;Hepatic enzymes (AST, ALT, GGT);Ammonia (NH3);Thymidine;Deoxyuridine Lactate;Pyruvate;lactate/pyruvate ratio;Leukocyte Coenzyme Q10;Amino acids(emphasis on alanine, alanine/lysine ratio, alanine/phenylalanine+lysine ratio, alanine/phenylalanine+lysine ratio, citrulline);Carnitine levels;CPK;Creatine;Free glutathione (fGSH);oxidized disulfide (GSSG);fGSH/GSSG ratio;Plasma carbonyl content;Fibroblast growth factor 21 (fgf21);Metabolic profiling;Hepatic enzymes (AST, ALT, GGT);Ammonia (NH3);Thymidine;Deoxyuridine Alphanumeric "Suomalainen, A., Biomarkers For Mitochondrial Respiratory Chain Disorders. J Inherit Metab Dis, 2011. 34(2): P. 277-82. Haas, R.H., et al., Mitochondrial Disease: A Practical Approach for Primary Care Physicians. Pediatrics, 2007. 120(6): P. 1326-33. Mancuso, M., et al., Diagnostic Approach to Mitochondrial Disorders: The Need for a Reliable Biomarker. Curr Mol Med, 2009. 9(9): P. 1095-107. Davis, R.L., et al., Fibroblast Growth Factor 21 is a Sensitive Biomarker of Mitochondrial Disease. Neurology, 2013. 81(21): P. 1819-26. Atkuri, K.R., et al., Inherited Disorders Affecting Mitochondrial Function are Associated with Glutathione Deficiency and Hypocitrullinemia. Proc Natl Acad SCI U S A, 2009. 106(10): P. 3941-5. Longo, N., C. Amat Di San Filippo, and M. Pasquali, Disorders of Carnitine Transport and the Carnitine Cycle. Am J Med Genet C Semin Med Genet, 2006. 142C(2): P. 77-85. Shaham, O., et al., A Plasma Signature of Human Mitochondrial Disease Revealed Through Metabolic Profiling of Spent Media from Cultured Muscle Cells. Proc Natl Acad SCI U S A, 2010. 107(4): P. 1571-5. Frye, R.E., Et al., Redox Metabolism Abnormalities in Autistic Children Associated with Mitochondrial Disease. Transl Psychiatry, 2013. 3: P. E273. Ribas, V., C. Garcia-Ruiz, and J.C. Fernandez-Checa, Glutathione and Mitochondria. Front Pharmacol, 2014. 5: P. 151. Chau, M.D., et al., Fibroblast Growth Factor 21 Regulates Energy Metabolism by Activating the AMPK-SIRT1-PGC-1ALPHA Pathway. Proc Natl Acad SCI U S A, 2010. 107(28): P. 12553-8. Gavrilova, R. and R. Horvath, Fibroblast Growth Factor 21, a Biomarker for Mitochondrial Muscle Disease. Neurology, 2013. 81(21): P. 1808-9. Liang, C., K. Ahmad, and C.M. Sue, The Broadening Spectrum of Mitochondrial Disease: Shifts in the Diagnostic Paradigm. Biochim Biophys Acta, 2014. 1840(4): P. 1360-1367. Su, S.L., et al., FGF21 iN Ataxia Patients with Spinocerebellar Atrophy and Mitochondrial Disease. Clin Chim Acta, 2012. 414: P. 225-7. Suomalainen, A., Fibroblast Growth Factor 21: A Novel Biomarker for Human Muscle-Manifesting Mitochondrial Disease. Expert Opin Med Diagn, 2013. 7(4): P. 313-7. Suomalainen, A., et al., FGF-21 as a Biomarker for Muscle-Manifesting Respiratory Chain Deficiencies: A Diagnostic Study. Lancet Neurol, 2011. 10(9): P. 806-18. Turnbull, D., A New Biomarker for Mitochondrial Disease. Lancet Neurol, 2011. 10(9): P. 777-8. Tyynismaa, H., et al., Mitochondrial Myopathy Induces a Starvation-like Response. Hum Mol Genet, 2010. 19(20): P. 3948-58. Valentino, M.L., et al., Thymidine and Deoxyuridine Accumulate in Tissue of Patients with Mitochondial Neurogastrointestinal Encephalomyopathy (MNGIE). Febs Lett, 2007. 581(18): P. 3410-4. Lara, M.C., et al., Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Biochemical Features and Therapeutic Approaches. Biosci Rep, 2007. 27(1-3): P. 151-63." Adult;Pediatric Supplemental 1.00 2014-12-18 15:54:03.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19562 Biomarker lymphocyte assessment type BiomarkLymohAssessTyp Type of biomarker(s) assessed from lymphocytes samples. Type of biomarker(s) assessed from lymphocytes samples. Which biomarker(s) were assessed from the specimen's lymphocytes sample? OXPHOS enzymology;High resolution respirometry;Coenzyme Q10;Intracellular glutathione;DNA strand breaks by comet assay (cultured cells);Micronucleus assay followed by fluorescense in situ hybridisation;pyruvate dehydrogenase OXPHOS enzymology;High resolution respirometry;Coenzyme Q10;Intracellular glutathione;DNA strand breaks by comet assay (cultured cells);Micronucleus assay followed by fluorescense in situ hybridisation;pyruvate dehydrogenase Alphanumeric Atkuri, K.R., et al., Inherited Disorders Affecting Mitochondrial Function are Associated with Glutathione Deficiency and Hypocitrullinemia. Proc Natl Acad SCI U S A, 2009. 106(10): P. 3941-5. Kramer, P.A., et al., A Review of the Mitochondrial and Glcolytic Metabolism in Human Platelets and Leukocytes: Implications for their Use as Bioenergetic Biomarkers. REdox Biol, 2014. 2: P. 206-210. Tomasetti, M., et al., Coenzyme Q10 Enrichment Decreases Oxidative DNA Damage in Human Lymphocytes. Free Radic Biol Med, 1999. 27(9-10): P. 1027-32. Migliore, L., ET AL., Evaluation of Cytogenetic and DNA Damage in Mitochondrial Disease Patients: Effects of Coenzyme Q10 Therapy. Mutagenesis, 2004. 19(1): P. 43-9. Naccarati, A., ET AL., Cytogenetic Damage in Peripheral Lympocytes of Mitochondrial Disease Patients. Neurol SCI, 2000. 21(5 SUPPL): P. S963-5. Vallance, H.D., J.R. Toone, and D.A. Applegarth, Measurement of Pyruvate Dehydrogenase (PDHC) in Interleukin-2 (IL-2) Stimulated Lymphocytes. J Inherit Metab Dis, 1994. 17(5): P. 627-8. Fouque, F., et al., Differential Effect of DCA Treatment on the Pyruvate Dehydrogenase Complex in Patients with Severe PDHC Deficiency. Pediatr Res, 2003. 53(5): P. 793-9. Adult;Pediatric Supplemental 1.00 2014-12-19 10:58:52.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19552 Blood specimen lactate measurement status BloodSpeclacMeasrStat The status related to lactate level measured from the specimen's blood serum/plasma sample. The status related to lactate level measured from the specimen's blood serum/plasma sample. Lactate accumulation level Increase in lactate;Normal lactate;Decrease in lactate Increase in lactate;Normal lactate;Decrease in lactate Alphanumeric "Suomalainen, A., Biomarkers For Mitochondrial Respiratory Chain Disorders. J Inherit Metab Dis, 2011. 34(2): P. 277-82. Haas, R.H., et al., Mitochondrial Disease: A Practical Approach for Primary Care Physicians. Pediatrics, 2007. 120(6): P. 1326-33. Mancuso, M., et al., Diagnostic Approach to Mitochondrial Disorders: The Need for a Reliable Biomarker. Curr Mol Med, 2009. 9(9): P. 1095-107. Davis, R.L., et al., Fibroblast Growth Factor 21 is a Sensitive Biomarker of Mitochondrial Disease. Neurology, 2013. 81(21): P. 1819-26." Adult;Pediatric Supplemental 1.00 2014-12-18 15:58:14.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Single Pre-Defined Value Selected

C19563 Biomarker lymphoblast assessment type BiomarkLymphAssessTyp Type of biomarker(s) assessed from lymphoblasts samples. Type of biomarker(s) assessed from lymphoblasts samples. Which biomarker(s) were assessed from the specimen's lymphoblast sample? ATP synthesis;High resolution respirometry ATP synthesis;High resolution respirometry Alphanumeric Van Bergen, N.J., et al., Oxidative Phosphorylation Measurement in Cell Lines and Tissues. Mitochondrion, 2014. Adult;Pediatric Supplemental 1.00 2014-12-19 11:04:10.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19553 Blood specimen pyruvate measurement status BloodSpecPyrMeasrStat The status as related to pyruvate level measured from the specimen's blood serum/plasma sample. The status as related to pyruvate level measured from the specimen's blood serum/plasma sample. Pyruvate accumulation level Increase in pyruvate;Normal pyruvate;Decrease in pyruvate Increase in pyruvate;Normal pyruvate;Decrease in pyruvate Alphanumeric "Suomalainen, A., Biomarkers For Mitochondrial Respiratory Chain Disorders. J Inherit Metab Dis, 2011. 34(2): P. 277-82. Haas, R.H., et al., Mitochondrial Disease: A Practical Approach for Primary Care Physicians. Pediatrics, 2007. 120(6): P. 1326-33. Mancuso, M., et al., Diagnostic Approach to Mitochondrial Disorders: The Need for a Reliable Biomarker. Curr Mol Med, 2009. 9(9): P. 1095-107. Davis, R.L., et al., Fibroblast Growth Factor 21 is a Sensitive Biomarker of Mitochondrial Disease. Neurology, 2013. 81(21): P. 1819-26." Adult;Pediatric Supplemental 1.00 2014-12-18 16:10:27.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Single Pre-Defined Value Selected

C19564 Biomarker muscle biochemistry assessment type BiomarkMuscBiochAssessTyp Type of biomarker(s) assessed from muscle biochemistry. Type of biomarker(s) assessed from muscle biochemistry. Which biomarker(s) were assessed from the specimen's muscle biochemsitry? OXPHOS enzymology;High resolution respirometry;mtDNA copy number;mtDNA deletion/duplication;pyruvate dehydrogenase enzymology;pyruvate dehydrogenase subunit western blot;Coenzyme Q10;Glutathione;OXPHOS subunit western blot;Blue native gel electrophoresis;clear native gel OXPHOS immunoblot;clear native gel OXPHOS enzymology;Human mitochondrial transcription factor A (hmTFA or Tfam);Mitochondrial DNA absence factor (midas);Biogenesis regulator peroxisome proliferator-activated receptor-gamma coactivator- 1 alpha (PGC-1alpha);8-oxoguanine DNA glycolase-1 (OCG-1);Manganese superoxide dismutase (MnSOD);AIF;Bcl-2;Aconitase enzymology OXPHOS enzymology;High resolution respirometry;mtDNA copy number;mtDNA deletion/duplication;pyruvate dehydrogenase enzymology;pyruvate dehydrogenase subunit western blot;Coenzyme Q10;Glutathione;OXPHOS subunit western blot;Blue native gel electrophoresis;clear native gel OXPHOS immunoblot;clear native gel OXPHOS enzymology;Human mitochondrial transcription factor A (hmTFA or Tfam);Mitochondrial DNA absence factor (midas);Biogenesis regulator peroxisome proliferator-activated receptor-gamma coactivator- 1 alpha (PGC-1alpha);8-oxoguanine DNA glycolase-1 (OCG-1);Manganese superoxide dismutase (MnSOD);AIF;Bcl-2;Aconitase enzymology Alphanumeric Van Den Heuvel, L.P., J.A. Smeitink, and R.J. Rodenburg, Biochemical Examination of Fibroblasts in the Diagnosis and Research of Oxidative Phosphorylation (OXPHOS) Defects. Mitochondrion, 2004. 4(5-6): P. 395-401. Schwab M.A., et al., Optimized Spctrophotometric Assay for the Completely Activated Pyruvate Dehydrogenase Complex in Fibroblasts. Clin Chem, 2005. 51(1): P. 151-60. Capaldi, R.A., et a;., Immunological Approaches to the Characterization and Diagnosis of Mitochondrial Disease. Mitochondrion, 2004. 4(5-6): P. 417-26. Calvaruso, M.A., J. Smeitink, AND L. Nijtmans, Electrophoresis Techniques to Investigate Defects in Oxidative Phosphorylation. MEthods, 2008. 46(4): P. 281-7. Carrozzo, R., ET AL., Subcomplexes of Human ATP Synthase Mark Mitochondrial Biosynthesis Disorders. Ann Neurol, 2006. 59(2): P. 265-75. Dimauro, S., C.M. Quinzii, and M. Hirano, Mutations in Coenzynme Q10 Biosynthetic Genes. J Clin Invest, 2007. 117(3): P. 587-9. Lopez, L.C., et al., Leigh Syndrome with Nephropathy and COQ10 Deficiency Due to Decarpenyl Diphosphate Synthase Subunit 2 (PDSS2) Mutations. Am J Hum Genet, 2006. 79(6): P. 1125-9. Adeva, M., et al., Enzymes Involved in L-lactate Metabolism in Humans. Mitochondrion, 2013. 13(6): P. 615-29. Hargreaves, I.P., et al., Glutathione Deficiency in Patients with Mitochondrial Disease: Implications for a Patho, 2005. 28(1): P. 81-8. Comi, G.P., et al., Cytochrome c Oxidase Subunit I Microdeletion in a Patient with Motor Neuron Disease. Ann Neurol, 1998. 43(1): P. 110-6. Andringa, K., A. King, and S. Bailey, Blue Native-gel Electrophoresis Prteomics. Methods Mol Biol, 2009. 519: P. 241-58. Tuppen, H.A., et al., Mutations in the Mitochondrial tRNA Ser(agy) Gene are Associated with Deafness, Retinal Degeneration, Myopathy and Epilepsy. Eur J Hum Genet, 2012. 20(8): P. 897-904. Assouline, Z., et al., A Constant and Similar Assembly Defect of Mitochonrial Respiratory Chain Complex I Allows Rapid Identification of NDUFS4 Mutations in Patients with Leigh Syndrome. Biobhim Biophys Acta, 2012. 1822(6): P. 1062-9. Pitceathly, R.D., et al., Kearns-Sayre Syndrome Caused by Defective R1/P53R2 Assembly. J Med Genet, 2011. 48(9): P. 610-7. Gerards, M., et al., Defective Complex I Assembly Due to C20ORF7 Mutations as a New Cause of Leigh Syndrome. J Med Genet, 2010. 47(8): P. 507-12. Wittig, I. and H. Schagger, Features and Applications of Blue-native and Clear-native Electrophoresis. Proteomics, 2008. 8(19): P. 3974-90. Wittig, I. and H. Schagger, Advantages and Limitations of Clear-native PAGE. Proteomics, 2005. 5(17): P. 4338-46. Wumaier, Z., et al., Chapter 8 Two-Dimensional Native Electrophoresis for Flourescent and Functional Assays of Mitochondrial Complexes. Methods Enzymol, 2009. 456: P. 153-68. Wittig, I., et al., Functional Assays in High-resolutio Clear Native Gels to Quantify Mitochondrial Complexes in Human Biopsies and Cell Lines. Electrphoresis, 2007. 28(21): P. 3811-20. Wittig, I., M. Karas, and H. Schagger, High Resolution Clear Native Electrophoresis for in-gel Functional Assays and Flourescence Studies of Membrane Protein Complexes. Mol Cell Proteomics, 2007. 6(7): P. 1215-25. Siciliano, G., et al., Abnormal Levels of Human Mitochondrial Transcription Factor A in Skeletal Muscle in Mitochondrial Encephalomyopathies. Neurol SCI, 2000. 21(5 SUPPL): P. S985-7. Nakashima-Kamimura N., et al., MIDAS/GPP34, A Nuclear Gene Product, Regulates Total Mitochondrial Mass in Response to Mitochondrial Dysfunction. J Cell SCI, 2005. 118(PT 22): P. 5357-67. Adhihetty, P.J., et al., The Effect of Training on the Expression of Mitochondrial Biogenesis- and Apoptosis-related Proteins in Skeletal Muscle of Patients with mtDNA Defects. Am J Physiol Endocrinol Metab, 2007. 293(3): P. E672-80. Adult;Pediatric Supplemental 1.00 2014-12-19 11:06:43.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19554 Blood specimen lactate pyruvate ratio status BloodSpecLacPyrRatStat The status as related to lactate/pyruvate ratio level measured from the specimen's blood serum/plasma sample. The status as related to lactate/pyruvate ratio level measured from the specimen's blood serum/plasma sample. Lactate/pyruvate ratio level Increase in L:P ratio;Normal L:P ratio;Decrease in L:P ratio Increase in L:P ratio;Normal L:P ratio;Decrease in L:P ratio Alphanumeric "Suomalainen, A., Biomarkers For Mitochondrial Respiratory Chain Disorders. J Inherit Metab Dis, 2011. 34(2): P. 277-82. Haas, R.H., et al., Mitochondrial Disease: A Practical Approach for Primary Care Physicians. Pediatrics, 2007. 120(6): P. 1326-33. Mancuso, M., et al., Diagnostic Approach to Mitochondrial Disorders: The Need for a Reliable Biomarker. Curr Mol Med, 2009. 9(9): P. 1095-107. Davis, R.L., et al., Fibroblast Growth Factor 21 is a Sensitive Biomarker of Mitochondrial Disease. Neurology, 2013. 81(21): P. 1819-26." Adult;Pediatric Supplemental 1.00 2014-12-18 17:00:54.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Single Pre-Defined Value Selected

C19567 Biomarker muscle histology assessment type BiomarkMuscHistAssessTyp Type of biomarker(s) assessed from muscle histology. Type of biomarker(s) assessed from muscle histology. Which biomarker(s) were assessed from the specimen's muscle histology? Gomori trichrome;succinate dehydrogenase (SDH);Cytochrome c Oxidase (COX) (Complex IV);Combined SDH+COX;Fibroblast growth factor 21 (fg21);OXPHOS subunit immunochemistry;Humanin immunochemistry Gomori trichrome;succinate dehydrogenase (SDH);Cytochrome c Oxidase (COX) (Complex IV);Combined SDH+COX;Fibroblast growth factor 21 (fg21);OXPHOS subunit immunochemistry;Humanin immunochemistry Alphanumeric Davis, R.L., et al., Fibroblast Growth Factor 21 is a Sensitive Biomarker of Mitochondrial Disease. Neurology, 2013. 81(21): P. 1819-26. Suomalainen, A., et al., FGF-21 as a Biomarker for Muscle-Manifesting Respiratory Chain Deficiencies: A Diagnostic Study. Lancet Neurol, 2011. 10(9): P. 806-18. Tyynismaa, H., et al., Mitochondrial Myopathy Induces a Starvation-like Response. Hum Mol Genet, 2010. 19(20): P. 3948-58. Filosto, M., et al., Neuropathology of Mitochondrial Diseases. Biosci Rep, 2007. 27(1-3): P. 23-30. Ross, J.M., Visualization of Mitochondrial Respiratory Function Using Cytochrome C Oxidase/Succinate Dehydrogenase (COX/SDH) Double-labeling Histochemistry. J Vis Exp, 2011(57): P. E3266. De Paepe, B., et al., Immunohistochemical Analysis of the Oxidative Phosphorylation Complexes in Skeletal Muscle from Patients with Mitochondrial DNA Encoded tRNA gene Defects. J Clin Pathol, 2009. 62(2): P. 172-6. Kin, T., et al., Humanin Expression in Skeletal Muscles of Patients with Chronic Progressive Extrenal Ophthalmoplegia. J Hum Genet, 2006. 51(6): P. 555-8. Adult;Pediatric Supplemental 1.00 2014-12-19 11:50:51.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19555 Biomarker Urine Assessment Type BiomarkUrineAssessTyp Type of biomarker(s) assessed from urine samples. Type of biomarker(s) assessed from urine samples. Which biomarker(s) were assessed from the specimen's urine sample? Organic acids;3-methylglutaconic acid;amino acids;Lactate/creatinine Organic acids;3-methylglutaconic acid;amino acids;Lactate/creatinine Alphanumeric "Suomalainen, A., Biomarkers For Mitochondrial Respiratory Chain Disorders. J Inherit Metab Dis, 2011. 34(2): P. 277-82. Haas, R.H., et al., Mitochondrial Disease: A Practical Approach for Primary Care Physicians. Pediatrics, 2007. 120(6): P. 1326-33. Barshop, B.A., Metabolomic Approaches to Mitochondrial Disease: Correlation of Urine Organic Acids. Mitochondrion, 2004. 4(5-6): P. 521-7. Wortmann, S., et al., Association with 3-Methylglutaconic Aciduria with Sensori-Neural Deafness, Encephalopathy, and Leigh-like Syndrome (MEGDEL Association) in Four Patients with a Disorder of Oxidative Phosphorylation. Mol Genet Metab, 2006. 88(1): P. 47-52. Wortmann, S., et al., Biochemical and Genetic Analysis of 3-Methylglutaconic Aciduria Type IV: A Diagnostic Stategy. Brain, 2009. 132(PT 1): P. 136-46." Adult;Pediatric Supplemental 1.00 2014-12-18 17:09:07.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19568 Biomarker myotube assessment type BiomarkerMyotAssessTyp Type of biomarker(s) assessed nfrom myotubes. Type of biomarker(s) assessed nfrom myotubes. Which biomarker(s) were assessed from the specimen's myotubes? Metabolic profiling;High resolution respirometry Metabolic profiling;High resolution respirometry Alphanumeric Shaham, O., et al., A Plasma Signature of Human Mitochondrial Disease Revealed Through Metabolic Profiling of Spent Media from Cultured Muscle Cells. Proc Natl Acad SCI U S A, 2010. 107(4): P. 1571-5. Adult;Pediatric Supplemental 1.00 2014-12-19 12:04:16.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19556 Biomarker cerebrospinal fluid assessment type BiomarkCerebrospFluAssessTyp Type of biomarker assessed from CSF samples Type of biomarker assessed from CSF samples Which biomarker(s) were assessed from the specimen's cerebrospinal fluid (CSF) sample? Lactate;Pyruvate;lactate/pyruvate ratio;Amino acids(emphasis on alanine, alanine/lysine ratio, alanine/phenylalanine+lysine ratio, alanine/phenylalanine+lysine ratio, citrulline);cell count;CSF protein;glucose (with simultaneous blood glucose) Lactate;Pyruvate;lactate/pyruvate ratio;Amino acids(emphasis on alanine, alanine/lysine ratio, alanine/phenylalanine+lysine ratio, alanine/phenylalanine+lysine ratio, citrulline);cell count;CSF protein;glucose (with simultaneous blood glucose) Alphanumeric "Suomalainen, A., Biomarkers For Mitochondrial Respiratory Chain Disorders. J Inherit Metab Dis, 2011. 34(2): P. 277-82. Haas, R.H., et al., Mitochondrial Disease: A Practical Approach for Primary Care Physicians. Pediatrics, 2007. 120(6): P. 1326-33. Benoist, J.F., et al., Cerebrospinal Fluid Lactate and Pyruvate Concentrations and their Ratio in Children: Age-related Reference Intevals. Clin Chem, 2003. 49(3): P. 487-94. Leen, W.G., et al., Cerebrospinal Fluid Analysis in the Workup of GLUT1 Deficiency Syndorme: A Systematic Review. Jama Neurol, 2013. 70(11): P. 1440-4." Adult;Pediatric Supplemental 1.00 2014-12-18 17:13:41.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19569 Biomarker genetic assessment type BiomarkGenetAssessTyp The types of genetic biomarker from the speciment that were evaluated. The types of genetic biomarker from the speciment that were evaluated. Which biomarker(s) were assessed from the specimen's genetics? Cellular energetics gene sequencing (NGS) (nDNA +mtDNA);mtDNA sequencing;Exome sequencing (NGS) (nDNA);mtDNA deletion/duplication (Leukocytes);mtDNA deletion/duplication (muscle);mtDNA copy number (Leukocytes);mtDNA copy number (muscle);Mitochondrial haplotype;Mitochondrial gene expression profiling Cellular energetics gene sequencing (NGS) (Ndna +mtDNA);mtDNA sequencing;Exome sequencing (NGS) (nDNA);mtDNA deletion/duplication (Leukocytes);mtDNA deletion/duplication (muscle);mtDNA copy number (Leukocytes);mtDNA copy number (muscle);Mitochondrial haplotype;Mitochondrial gene expression profiling Alphanumeric Adult;Pediatric Supplemental 1.00 2014-12-19 15:45:40.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19557 Biomarker fibroblasts assessment type BiomarkFibroblAssessTyp Type of biomarker(s) assessed from fibroblasts samples. Type of biomarker(s) assessed from fibroblasts samples. Which biomarker(s) were assessed from the specimen's fibroblasts sample? High resolution respirometry;lactate/pyruvate ratio;OXPHOS enzymology;pyruvate dehydrogenase enzymology;pyruvate dehydrogenase subunit western blot;pyruvate dehydrogenase immunohistochemistry;ATP synthesis;Fibroblast OXPHOS subunit immunohistochemistry;OXPHOS subunit western blot;Blue native gel electrophoresis;clear native gel OXPHOS immunoblot;clear native gel OXPHOS enzymology;Coenzyme Q10 High resolution respirometry;lactate/pyruvate ratio;OXPHOS enzymology;pyruvate dehydrogenase enzymology;pyruvate dehydrogenase subunit western blot;pyruvate dehydrogenase immunohistochemistry;ATP synthesis;Fibroblast OXPHOS subunit immunohistochemistry;OXPHOS subunit western blot;Blue native gel electrophoresis;clear native gel OXPHOS immunoblot;clear native gel OXPHOS enzymology;Coenzyme Q10 Alphanumeric "Cameron, J.M., et al., Respiratory Chain Analysis of Skin Fibroblasts in Mitochondrial Disease. Mitochondrion, 2004. 4(5-6): P. 387-94. Van Den Heuvel, L.P., J.A. Smeitink, and R.J. Rodenburg, Biochemical Examination of Fibroblasts in the Diagnosis and Research of Oxidative Phosphorylation (OXPHOS) Defects. Mitochondrion, 2004. 4(5-6): P. 395-401. Cameron, J.M., et al., Deficiency of Pyruvate Dehydrogenase Caused by Novel and Known Mutations in the E1ALPHA Subunit. Am J Med Genet A, 2004. 131(1): P. 59-66. Schwab M.A., et al., Optimized Spctrophotometric Assay for the Completely Activated Pyruvate Dehydrogenase Complex in Fibroblasts. Clin Chem, 2005. 51(1): P. 151-60. Capaldi, R.A., et a;., Immunological Approaches to the Characterization and Diagnosis of Mitochondrial Disease. Mitochondrion, 2004. 4(5-6): P. 417-26. Shepherd, R.K., et al., Measurement of ATP Production in Mitochondrial Disorders. J Inherit Metab Dis, 2006. 29(1): P. 86-91. De Paepe, B., et al., Diagnostic Value of Immunostaining in Cultured Skin Fibroblasts from Patients with Oxidative Phosphorylation Defects. Pediatr Res, 2006. 59(1): P. 2-6. Calvaruso, M.A., J. Smeitink, AND L. Nijtmans, Electrophoresis Techniques to Investigate Defects in Oxidative Phosphorylation. MEthods, 2008. 46(4): P. 281-7. Carrozzo, R., ET AL., Subcomplexes of Human ATP Synthase Mark Mitochondrial Biosynthesis Disorders. Ann Neurol, 2006. 59(2): P. 265-75. Dimauro, S., C.M. Quinzii, and M. Hirano, Mutations in Coenzynme Q10 Biosynthetic Genes. J Clin Invest, 2007. 117(3): P. 587-9. Lopez, L.C., et al., Leigh Syndrome with Nephropathy and COQ10 Deficiency Due to Decarpenyl Diphosphate Synthase Subunit 2 (PDSS2) Mutations. Am J Hum Genet, 2006. 79(6): P. 1125-9. Mollet, J., et al., Prenyldiphosphate Synthase Subunit 1 (PDSS1) And OH-Benzoate Polyprenyltransferase (COQ2) Mutations in Ubiquinone Deficiency and Oxidative Phosphorylation Disorders. J Clin Invest, 2007. 117(3): P. 765-72. Quinzii, C., et al., A Mutation in Para-hydroxybenzoate-polprenyltransferase (COQ2) Causes Primary Coenzyme Q10 Deficiency. Am J Hum Genet, 2006. 78(2): P. 345-9." Adult;Pediatric Supplemental 1.00 2014-12-18 17:18:31.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19558 Biomarker leukocytes assessment type BiomarkLeukoAssessTyp Type of biomarker(s) assessed from leukocytes samples. Type of biomarker(s) assessed from leukocytes samples. Which biomarker(s) were assessed from the specimen's leukocytes sample? Intracellular free glutathione;Intracellular coenzyme Q10;pyruvate dehydrogenase enzymology;Thymidine phosphorylase enzymology;Coenzyme Q10;mtDNA deletion/duplication;mtDNA copy number Intracellular free glutathione;Intracellular coenzyme Q10;pyruvate dehydrogenase enzymology;Thymidine phosphorylase enzymology;Coenzyme Q10;mtDNA deletion/duplication;mtDNA copy number Alphanumeric "Atkuri, K.R., et al., Inherited Disorders Affecting Mitochondrial Function are Associated with Glutathione Deficiency and Hypocitrullinemia. Proc Natl Acad SCI U S A, 2009. 106(10): P. 3941-5. Valentino, M.L., et al., Thymidine and Deoxyuridine Accumulate in Tissue of Patients with Mitochondial Neurogastrointestinal Encephalomyopathy (MNGIE). Febs Lett, 2007. 581(18): P. 3410-4. Lara, M.C., et al., Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Biochemical Features and Therapeutic Approaches. Biosci Rep, 2007. 27(1-3): P. 151-63. Cordero, M.D., et al., Mitochondrial Dysfunction and Mitophagy Activation in Blood Mononuclear Cells of Fibromyalgia Patients: Implicatopns in the Pathogenesis of the Disease. Arthritis Res Ther, 2010. 12(1): P. R17. Duncan A.J., et al., Detrmination of Coenzyme Q10 Status in Blood Mononuclear Cells, Skeletal Muscle, and Plasma by HPLC with Di-propoxy-coenzyme Q10 as an Internal Standard. Clin Chem, 2005. 51(12): P. 2380-2. " Adult;Pediatric Supplemental 1.00 2014-12-19 10:36:45.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19559 Biomark neutrophils assessment type BiomarkNeutrAssessTyp Type of biomark(s) assessed from neutrophils sample Type of biomark(s) assessed from neutrophils sample Which biomarker(s) were assessed from the specimen's neutrophils sample? OXPHOS enzymology;High resolution respirometry;Coenzyme Q10;Intracellular glutathione OXPHOS enzymology;High resolution respirometry;Coenzyme Q10;Intracellular glutathione Alphanumeric Atkuri, K.R., et al., Inherited Disorders Affecting Mitochondrial Function are Associated with Glutathione Deficiency and Hypocitrullinemia. Proc Natl Acad SCI U S A, 2009. 106(10): P. 3941-5. Kramer, P.A., et al., A Review of the Mitochondrial and Glcolytic Metabolism in Human Platelets and Leukocytes: Implications for their Use as Bioenergetic Biomarkers. REdox Biol, 2014. 2: P. 206-210. Adult;Pediatric Supplemental 1.00 2014-12-19 10:47:13.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19548 Biomarker Analysis Indicator BiomarkAnaInd Indicator that a biomarker analysis was performed. Indicator that a biomarker analysis was performed. Was a biomarker analysis done? Yes;No Biomarker analysis was performed;Biomarker analysis was not perfomed Alphanumeric

If yes, please answer questions below:

Adult;Pediatric Supplemental 1.00 2014-12-15 14:56:57.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Single Pre-Defined Value Selected

C19560 Biomarker monocyte assessment type BiomarkMonocAssessTyp Type of biomark(s) assessed from monocytes samples. Type of biomark(s) assessed from monocytes samples. Which biomarker(s) were assessed from the specimen's monocytes sample? OXPHOS enzymology;High resolution respirometry;Coenzyme Q10;Intracellular glutathione;Intracellular free glutathione (fGSH), oxidized disulfide (GSSG), fGSH/GSSG ratio;pyruvate dehydrogenase enzymology;Thymidine phosphorylase enzymology OXPHOS enzymology;High resolution respirometry;Coenzyme Q10;Intracellular glutathione;Intracellular free glutathione (fGSH), oxidized disulfide (GSSG), fGSH/GSSG ratio;pyruvate dehydrogenase enzymology;Thymidine phosphorylase enzymology Alphanumeric Atkuri, K.R., et al., Inherited Disorders Affecting Mitochondrial Function are Associated with Glutathione Deficiency and Hypocitrullinemia. Proc Natl Acad SCI U S A, 2009. 106(10): P. 3941-5. Valentino, M.L., et al., Thymidine and Deoxyuridine Accumulate in Tissue of Patients with Mitochondial Neurogastrointestinal Encephalomyopathy (MNGIE). Febs Lett, 2007. 581(18): P. 3410-4. Lara, M.C., et al., Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Biochemical Features and Therapeutic Approaches. Biosci Rep, 2007. 27(1-3): P. 151-63. Cordero, M.D., et al., Mitochondrial Dysfunction and Mitophagy Activation in Blood Mononuclear Cells of Fibromyalgia Patients: Implicatopns in the Pathogenesis of the Disease. Arthritis Res Ther, 2010. 12(1): P. R17. Duncan A.J., et al., Detrmination of Coenzyme Q10 Status in Blood Mononuclear Cells, Skeletal Muscle, and Plasma by HPLC with Di-propoxy-coenzyme Q10 as an Internal Standard. Clin Chem, 2005. 51(12): P. 2380-2. Kramer, P.A., et al., A Review of the Mitochondrial and Glcolytic Metabolism in Human Platelets and Leukocytes: Implications for their Use as Bioenergetic Biomarkers. REdox Biol, 2014. 2: P. 206-210. Adult;Pediatric Supplemental 1.00 2014-12-19 10:51:50.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Multiple Pre-Defined Values Selected

C19549 Biomarker Sample Assessment Type BiomarkSampAssessTyp Type of sample obtained from specimen to assess the biomarker Type of sample obtained from specimen to assess the biomarker Sample/method used to assess the biomarker Blood;Urine;CSF;Fibroblasts;Leukocytes;Neutrophils;Monocytes;Platelets (high OXPHOS);Lymphocytes;Lymphoblasts (EBV);Muscle biochemistry;Muscle histology;Myotubes;Liver histology;Liver biochemistry;Genetic Testing Blood (Serum/Plasma);Urine;Cerebrospinal fluid;Fibroblasts;Leukocytes;Neutrophils;Monocytes;Platelets (high OXPHOS);Lymphocytes;Lymphoblasts (EBV);Muscle biochemistry;Muscle histology;Myotubes;Liver histology;Liver biochemistry;Genetic Testing Alphanumeric Adult;Pediatric Supplemental 1.00 2014-12-15 14:56:57.0 Biomarkers in Mitochondrial Disease Laboratory Tests and Biospecimens/Biomarkers Assessments and Examinations

Single Pre-Defined Value Selected

CSV