| Clinical phenotype | Phenotype type | Suggested HPO term(s) | Typical onset/course | Brief notes | Supporting evidence snippet |
|---|---|---|---|---|---|
| Gastrointestinal dysmotility / chronic intestinal pseudo-obstruction (CIPO)-like disease | Symptom/sign | HP:0002579 Intestinal pseudo-obstruction; HP:0002014 Diarrhea; HP:0002017 Nausea; HP:0002015 Dysphagia; HP:0002027 Abdominal pain; HP:0002242 Vomiting | Usually begins in childhood, adolescence, or early adulthood; progressive and often severe | Hallmark feature of MNGIE; includes dysmotility, recurrent pseudo-obstruction, abdominal pain, vomiting, diarrhea, dysphagia, and severe nutritional compromise | “progressive gastrointestinal dysmotility”; “CIPO-like”; “gastrointestinal and ocular involvement are usually initial features” |
| Cachexia / severe weight loss | Symptom/sign | HP:0004326 Cachexia; HP:0001824 Weight loss; HP:0001510 Growth delay | Progressive over years; often worsens with GI disease | Major contributor to morbidity and mortality; may require enteral or parenteral nutritional support | “cachexia”; “severe denutrition”; “4 kg weight gain” after treatment indicates baseline wasting |
| Peripheral neuropathy | Clinical sign / electrophysiologic abnormality | HP:0009830 Peripheral neuropathy; HP:0003401 Sensory neuropathy; HP:0003323 Peripheral axonal neuropathy; HP:0001270 Motor delay/weakness-related terms as applicable | Typically develops by teens to early adulthood; progressive | Often sensorimotor, causing paresthesias, weakness, gait impairment; supported by NCS/EMG | “peripheral neuropathy”; “stocking-glove paresthesia and weakness”; “electrophysiologically confirmed peripheral neuropathy” |
| External ophthalmoplegia / ophthalmoparesis | Clinical sign | HP:0000602 Ophthalmoplegia; HP:0000601 Impaired ocular motility | Common early neurologic feature; slowly progressive | Part of the classic phenotype; may accompany ptosis and chronic progressive external ophthalmoplegia-like presentation | “ophthalmoplegia”; “external ophthalmoparesis”; “CPEO” |
| Ptosis | Clinical sign | HP:0000508 Ptosis | Often early; progressive | Frequently co-occurs with ophthalmoplegia and may be a presenting clue | “ptosis” |
| Diffuse leukoencephalopathy on brain MRI | Imaging abnormality | HP:0002352 Leukoencephalopathy; HP:0002500 Abnormal cerebral white matter morphology | Often present by time of diagnosis; usually progressive radiologically but may be clinically silent | Characteristic MRI pattern with white-matter T2/FLAIR hyperintensities; cognition often relatively spared | “diffuse leukoencephalopathy”; “MRI shows leukoencephalopathy while cognition is generally spared” |
| Hearing loss / sensorineural deafness | Symptom/sign | HP:0000407 Sensorineural hearing impairment; HP:0000365 Hearing impairment | Variable; can appear early or later in disease course | Not universal but repeatedly reported; may broaden suspicion beyond classic tetrad | “hearing loss”; “deafness”; “reported in 61% of patients” |
| Skeletal myopathy / exercise intolerance / weakness | Symptom/sign / pathology-supported feature | HP:0003323 Myopathy; HP:0001324 Muscle weakness; HP:0003546 Exercise intolerance | Progressive, often alongside neuropathy | Reflects secondary mitochondrial dysfunction; may show ragged-red or COX-deficient fibers on muscle biopsy | “skeletal myopathy”; “improved strength and mobility”; “ragged red fibers” |
| Elevated CSF protein | Laboratory abnormality | HP:0012116 Abnormal cerebrospinal fluid protein level; HP:0002922 Increased CSF protein | Can be detected during workup; not necessarily symptomatic | Helpful supportive biomarker in differential diagnosis | “CSF protein is often elevated (typically 60–100 mg/dL)” |
| Lactic acidosis / elevated lactate | Laboratory abnormality | HP:0003128 Lactic acidosis; HP:0011013 Abnormality of metabolic homeostasis | Variable; may fluctuate with disease burden | Supports mitochondrial dysfunction but is not specific to MNGIE | “lactic acidosis”; “elevated lactate” |
| Cognitive preservation despite MRI abnormalities | Clinical characteristic | HP:0000729 Autistic behavior not applicable; no precise HPO for preserved cognition; consider phenotype note only | Often persistent across course | Important distinguishing feature: marked white-matter disease may occur with limited overt encephalopathy | “cognition is generally spared” |
| Mitochondrial muscle pathology | Pathology finding | HP:0003200 Rigid spine not applicable; use pathology note with HP:0008322 Abnormal muscle biopsy | Appears in established disease | Muscle biopsy may show ragged-red fibers, COX-deficient fibers, and mtDNA deletions/depletion | “ragged red fibers, cytochrome c oxidase-deficient fibers”; “mtDNA deletions/depletions” |
| Gastrointestinal bacterial overgrowth / nutritional failure complications | Complication | HP:0011968 Malnutrition; HP:0004395 Small intestinal bacterial overgrowth | Usually later-stage or secondary to severe dysmotility | Contributes to poor quality of life and treatment complexity | “small intestinal bacterial overgrowth”; need for “TPN” / nutritional support |


*Table: This table summarizes the main clinical and laboratory phenotypes reported for MNGIE, with suggested HPO mappings and concise notes on onset and progression. It is useful as a phenotype-to-ontology scaffold for disease knowledge base curation.*