IEMbase 0024: MAT1A-related methionine adenosyltransferase I-III deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 24 |
| Nosology | 1.5.01.01 |
| Gene | MAT1A |
| External IDs | OMIM:250850 |
| Generated mapping | MAPPED by alias_exact:methionine adenosyltransferase i iii deficiency |
| Candidate DisMech targets | Inborn_Disorder_of_Methionine_Cycle_and_Sulfur_Amino_Acid_Metabolism.yaml#MAT I/III deficiency |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase presents MAT I/III deficiency as a hypermethioninemia/SAM-synthesis disorder. Characteristic clinical signals are cabbage-like breath odor from dimethylsulfide and vacuolating myelopathy. Additional neurologic findings include cognitive dysfunction, developmental delay, language difficulties, demyelination, dystonia, tremor, dysdiadochokinesis, dysmetria, headache, nystagmus, and increased tendon reflexes.
The biochemical signature is high plasma methionine, high methionine-to-cystathionine and methionine-to-total-homocysteine ratios, elevated urinary methionine sulfoxide, normal S-adenosylhomocysteine, and low-to-normal S-adenosylmethionine. IEMbase lists no treatment rows for this record.
DisMech phenotype coverage
The generated subtype mapping is correct. DisMech models MAT I/III deficiency under the methionine-cycle and sulfur amino-acid metabolism umbrella, with a MAT1A subtype, persistent isolated hypermethioninemia, impaired S-adenosylmethionine synthesis, risk of cerebral white-matter injury, delayed language development, and therapies including low-methionine diet, S-adenosylmethionine/ademetionine supplementation, and liver transplantation for severe refractory disease.
Concordance and completeness
Judgement: correct mapping with good biochemical concordance, but IEMbase has more granular neurologic phenotype detail.
DisMech captures the central mechanism and the core severe phenotype of hypermethioninemia-associated white-matter injury. IEMbase adds the cabbage-like odor, vacuolating myelopathy, cerebellar/extrapyramidal signs, nystagmus, hyperreflexia, and several useful ratio markers. Conversely, DisMech is more complete for therapy and mechanism.
Curation actions
- Keep the generated subtype mapping.
- Consider adding the odor, myelopathy, and movement/cerebellar signs to the MAT I/III subtype if supported by evidence.
- Consider whether IEMbase ratio markers and urinary methionine sulfoxide should be added as subtype-specific biochemical markers.