IEMbase 0025: GNMT-related glycine N-methyltransferase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 25 |
| Nosology | 1.5.03.01 |
| Gene | GNMT |
| External IDs | OMIM:606664 |
| Generated mapping | UNMAPPED; best fuzzy candidate Guanidinoacetate_Methyltransferase_Deficiency.yaml |
| Candidate DisMech targets | none currently valid |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents glycine N-methyltransferase deficiency as a sulfur amino-acid/methylation disorder. The clinical signal is sparse: possible failure to thrive in infancy and possible hepatomegaly in infancy or childhood.
The biochemical signal is much stronger than the clinical signal: markedly elevated plasma methionine, markedly elevated plasma S-adenosylmethionine, normal S-adenosylhomocysteine, normal urinary sarcosine, normal-to-mildly high total plasma homocysteine, and mild transaminase elevation. No treatment rows are present and treatability is listed as unknown.
DisMech phenotype coverage
There is no current standalone DisMech entry or subtype for GNMT deficiency. The
best fuzzy candidate, Guanidinoacetate_Methyltransferase_Deficiency.yaml, is a
false positive driven by the word methyltransferase. GAMT deficiency is a
cerebral creatine deficiency disorder with guanidinoacetate accumulation,
creatine depletion, epilepsy, developmental delay, and creatine/substrate
reduction therapy. That is not the same disease mechanism or phenotype pattern
as GNMT-related hypermethioninemia and elevated SAM.
The broader methionine-cycle/sulfur amino-acid umbrella is conceptually closer than the fuzzy GAMT candidate, but it does not currently list GNMT deficiency as a subtype.
Concordance and completeness
Judgement: generated status is appropriately unmapped, and the fuzzy GAMT candidate should be rejected.
IEMbase supplies enough biochemical signal to define a future GNMT curation target, but there is no local phenotype completeness comparison to make against a valid DisMech disease entry. The closest local reusable context is the methionine-cycle pathway group, not GAMT deficiency.
Curation actions
- Do not map this record to
Guanidinoacetate_Methyltransferase_Deficiency.yaml. - Consider adding GNMT deficiency as a subtype or separate entry under the methionine-cycle/sulfur amino-acid area if it becomes a curation priority.
- Preserve the biochemical distinction from MAT1A and AHCY disease: high methionine and SAM with normal S-adenosylhomocysteine.