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IEMbase 0030: MTR-related methionine synthase deficiency

Scope

Field Value
IEMbase ID 30
Nosology 1.5.13.01
Gene MTR
External IDs OMIM:250940
Generated mapping MAPPED by alias_exact:cblg
Candidate DisMech targets Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#cblG
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents methionine synthase deficiency, cblG type. Characteristic features are megaloblastic anemia and neurologic symptoms. Additional features include developmental delay, failure to thrive, ataxia, cerebral atrophy on MRI, hypertonia or hypotonia, lethargy, adult myelopathy, nystagmus, psychiatric disturbance, seizures, impaired vision, and vomiting.

The biochemical signature is isolated remethylation failure: elevated urinary and plasma homocysteine, low-to-normal plasma methionine, normal plasma and urine methylmalonic acid, and low S-adenosylmethionine in CSF and plasma. Treatments listed are hydroxycobalamin and betaine.

DisMech phenotype coverage

The generated subtype mapping is correct. DisMech includes cblG as an MTR subtype within the cobalamin metabolism and transport umbrella. It models impaired methionine synthase activity/remethylation, homocystinuria, hyperhomocysteinemia, hypomethioninemia, megaloblastic anemia, intellectual disability, seizures, hypotonia, global developmental delay, encephalopathy, failure to thrive, and hydroxocobalamin/betaine therapy, with supportive avoidance of nitrous oxide and methionine restriction.

Concordance and completeness

Judgement: correct subtype mapping and good high-level concordance, but DisMech is currently more umbrella-level than cblG-specific.

IEMbase adds cblG-specific normal methylmalonic acid, low CSF/plasma SAM, cerebral atrophy, myelopathy, nystagmus, impaired vision, psychiatric disturbance, vomiting, and explicit hydroxycobalamin/betaine treatment rows. DisMech gives stronger mechanism and broader cobalamin-context coverage.

Curation actions

  • Keep the generated subtype mapping.
  • Consider adding cblG-specific normal methylmalonic acid and low SAM markers.
  • Consider whether cerebral atrophy, myelopathy, nystagmus, vision impairment, and vomiting should be added as cblG/cblE subtype-specific phenotypes.