IEMbase 0031: MTRR-related methionine synthase reductase deficiency, cblE
Scope
| Field | Value |
|---|---|
| IEMbase ID | 31 |
| Nosology | 21.9.12.01 |
| Gene | MTRR |
| External IDs | OMIM:236270 |
| Generated mapping | MAPPED by alias_exact:cble |
| Candidate DisMech targets | Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblE |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents methionine synthase reductase deficiency, cblE type. Characteristic features are megaloblastic anemia and neurologic symptoms. Additional clinical features include developmental delay, failure to thrive, ataxia, cerebral atrophy on MRI, hypertonia or hypotonia, adult myelopathy, nystagmus, psychiatric disturbance, seizures, and impaired vision.
The biochemical signal matches an isolated remethylation defect: elevated urine and plasma homocysteine, low-to-normal methionine, normal plasma and urinary methylmalonic acid, and low CSF/plasma S-adenosylmethionine. Treatments listed are hydroxycobalamin and betaine.
DisMech phenotype coverage
The generated subtype mapping is correct. DisMech includes cblE as an MTRR
subtype in Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml, models
the MTRR role in reductive reactivation of methionine synthase, and covers the
shared remethylation phenotype: homocystinuria, hyperhomocysteinemia,
hypomethioninemia, megaloblastic anemia, neurologic injury, developmental
delay, seizures, hypotonia, encephalopathy, failure to thrive, hydroxocobalamin,
and betaine.
Concordance and completeness
Judgement: correct subtype mapping and good high-level concordance, with the same subtype-granularity limitation seen for cblG.
IEMbase adds cblE-specific normal methylmalonic acid, low SAM in CSF/plasma, cerebral atrophy, myelopathy, nystagmus, impaired vision, psychiatric disturbance, and treatment rows. DisMech is stronger for pathway mechanism and the broader cobalamin-disorder context.
Curation actions
- Keep the generated subtype mapping.
- Consider adding cblE-specific biochemical markers and selected neurologic or imaging findings if evidence supports them.
- Keep cblE and cblG grouped as isolated remethylation defects, but avoid importing methylmalonic acidemia features from cblC/cblA/cblB.