| Diagnostic modality | What to test / finding | Specimen / source | Typical MNGIE result / threshold | Comparator / notes | Suggested ontology terms | Citation |
|---|---|---|---|---|---|---|
| Genetic testing | **TYMP** sequencing (biallelic pathogenic variants) | Genomic DNA from blood or other clinical specimen | Diagnostic benchmark is identification of homozygous or compound heterozygous **TYMP** variants | Primary causal gene for classic MNGIE; MNGIE-like phenotypes also reported with **POLG** and **RRM2B** | Gene: **TYMP**; MONDO: **MONDO_0017575** | (pqac-00000001, pqac-00000002, pqac-00000000) |
| Plasma nucleosides | Thymidine (dThd) and deoxyuridine (dUrd) quantification | Plasma | dThd **>3 µmol/L** and dUrd **>5 µmol/L** are characteristic; in some series patients have ~**10–20 µM** plasma nucleosides | Healthy individuals: both typically **<0.05 µmol/L** | CHEBI: thymidine, deoxyuridine | (pqac-00000001, pqac-00000002, pqac-00000009) |
| Urine nucleosides | Thymidine and deoxyuridine quantification | Urine / 24 h urine | Elevated urinary dThd/dUrd; reported diagnostic clues include urine dThd **>3 µmol/L** and dUrd **>5 µmol/L** | Can be followed longitudinally for treatment response | CHEBI: thymidine, deoxyuridine | (pqac-00000004, pqac-00000005) |
| Enzyme assay | Thymidine phosphorylase (TP) activity | Buffy coat leukocytes / leukocytes | Markedly reduced: reported **0–46 nmol thymidine formed/h/mg protein** or **<8–10% of controls** | Controls reported **253–1000 nmol/h/mg**; one source cites control mean ~**634 nmol thymine formed/h/mg protein**; heterozygotes may retain ~35% activity | GO: **thymidine phosphorylase activity**; Protein: TP | (pqac-00000001, pqac-00000004, pqac-00000005, pqac-00000008) |
| Neuroimaging | Brain MRI | Brain white matter | Diffuse leukoencephalopathy; typically **T1 hypointense** and **T2 hyperintense** white-matter abnormalities | Often extensive and may be clinically asymptomatic | UBERON: brain white matter; SNOMED/term suggestion: leukoencephalopathy | (pqac-00000001, pqac-00000003, pqac-00000007) |
| Electrodiagnostics | EMG / nerve conduction studies (NCS) | Peripheral nerves / muscle | Supports peripheral neuropathy; electrophysiologically confirmed neuropathy is a common diagnostic feature | Used as part of workup with clinical suspicion | UBERON: peripheral nerve, skeletal muscle | (pqac-00000001, pqac-00000002, pqac-00000031) |
| Muscle biopsy / histopathology | Ragged-red fibers, COX-deficient fibers, mtDNA abnormalities | Skeletal muscle biopsy | Mitochondrial pathology may show **ragged-red fibers**, **cytochrome c oxidase-deficient fibers**, and **mtDNA deletions/depletion** | Supportive rather than strictly required if biochemical/genetic diagnosis is established | UBERON: skeletal muscle; GO: mitochondrion; GO: mitochondrial DNA metabolic process | (pqac-00000001, pqac-00000007, pqac-00000013) |
| mtDNA analysis in muscle | mtDNA deletions / depletion testing | Skeletal muscle DNA | Secondary mitochondrial genome defects including **multiple deletions**, **point mutations**, and **mtDNA depletion** | Reflect downstream consequence of nucleoside imbalance rather than primary inherited mtDNA mutation | GO: mitochondrial DNA replication; GO: mitochondrion | (pqac-00000003, pqac-00000006, pqac-00000013) |
| CSF analysis | Cerebrospinal fluid protein | CSF | Often elevated; typically **60–100 mg/dL** | Supportive but nonspecific | UBERON: cerebrospinal fluid | (pqac-00000004, pqac-00000007) |
| Analytical platform notes | Nucleoside measurement methodology | Plasma / urine | Reported methods include **HPLC-UV** and **LC-MS/MS/UPLC** approaches for dThd/dUrd | Useful for reproducible biomarker monitoring in diagnosis and follow-up |  | (pqac-00000001, pqac-00000026) |


*Table: This table summarizes the principal diagnostic modalities for MNGIE, including genetic confirmation, hallmark nucleoside biomarkers, enzyme deficiency testing, imaging, electrophysiology, biopsy findings, and supportive CSF abnormalities. It is useful as a concise disease-knowledge-base artifact linking each test to specimen type, expected results, and ontology suggestions.*