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IEMbase 0157: TYMP-related MNGIE

Scope

Field Value
IEMbase ID 157
Nosology 9.1.08.01
Gene TYMP
External IDs OMIM:131222; OMIM:603041; ORPHA:298
Generated mapping AMBIGUOUS: Chronic_Intestinal_Pseudoobstruction.yaml#Mitochondrial; Mitochondrial_Neurogastrointestinal_Encephalomyopathy.yaml
Candidate DisMech targets Mitochondrial_Neurogastrointestinal_Encephalomyopathy.yaml; Chronic_Intestinal_Pseudoobstruction.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as TYMP-related thymidine phosphorylase deficiency, with alternate labels mitochondrial depletion syndrome 1, mitochondrial neurogastrointestinal encephalomyopathy syndrome, and MNGIE. Treatability is marked unknown.

The biochemical rows show markedly decreased WBC thymidine phosphorylase in adolescence and adulthood, increased plasma and urinary thymidine and 2'-deoxyuridine, and increased plasma lactate. The clinical profile includes abdominal pain, diarrhea, vomiting, gastrointestinal dysmotility, gastroparesis, malabsorption, chronic malnutrition, intestinal pseudo-obstruction, hypodense white matter/leukoencephalopathy, areflexia, myelinating neuropathy, muscle weakness, myopathy, and ragged-red fibers.

DisMech phenotype coverage

Mitochondrial_Neurogastrointestinal_Encephalomyopathy.yaml is the correct canonical target. It explicitly models classic TYMP-related MNGIE, thymidine phosphorylase deficiency, systemic thymidine and 2'-deoxyuridine accumulation, mitochondrial DNA depletion/deletions, gastrointestinal dysmotility, pseudo-obstruction, cachexia, ptosis/progressive external ophthalmoplegia, demyelinating peripheral neuropathy, leukoencephalopathy, skeletal myopathy, and disease-modifying approaches such as allogeneic hematopoietic stem cell transplantation, liver transplantation, erythrocyte-encapsulated thymidine phosphorylase, dialysis, and investigational gene therapy.

Chronic_Intestinal_Pseudoobstruction.yaml also has a mitochondrial subtype displayed as MNGIE and anchored on TYMP, but that entry is an umbrella CIPO entry. It is useful secondary context for the intestinal pseudo-obstruction phenotype, not the primary disease target for TYMP-related MNGIE.

Concordance and completeness

Judgement: generated ambiguity should resolve to the standalone MNGIE entry.

DisMech has strong concordance for gene, biochemical mechanism, nucleoside accumulation, gastrointestinal dysmotility, pseudo-obstruction, leukoencephalopathy, neuropathy, myopathy, and treatment mechanisms. IEMbase adds WBC enzyme activity as an explicit row, urinary thymidine/deoxyuridine, plasma lactate, areflexia, ragged-red fibers, and anorexia-nervosa wording as possible review details.

Curation actions

  • Map IEMbase 157 to Mitochondrial_Neurogastrointestinal_Encephalomyopathy.yaml.
  • Treat the CIPO mitochondrial subtype as secondary phenotype/subtype context, not as the canonical mapping.
  • Consider future refinement for urinary thymidine/deoxyuridine, WBC thymidine phosphorylase, plasma lactate, and ragged-red fiber rows.