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IEMbase 0085: TCN2-related transcobalamin II deficiency

Scope

Field Value
IEMbase ID 85
Nosology 21.9.05.01
Gene TCN2
External IDs OMIM:275350
Generated mapping MAPPED by alias_exact:tcn2 deficiency
Candidate DisMech targets Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#TCN2 deficiency
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as autosomal recessive TCN2-related transcobalamin 2 deficiency, with alternate labels transcobalamin II deficiency, TCN2 deficiency, and TCD. Treatability is marked yes.

The characteristic biochemical signal includes low plasma vitamin B12, elevated plasma and urinary methylmalonic acid, urinary homocysteine, and elevated total plasma homocysteine.

Characteristic clinical rows include megaloblastic anemia, apathy, chronic diarrhea, and failure to thrive.

Treatment rows are cyanocobalamin and hydroxycobalamin.

DisMech phenotype coverage

The generated mapping to Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#TCN2 deficiency is correct.

DisMech represents transcobalamin II deficiency as a subtype of the broader cobalamin metabolism and transport umbrella. The local pathophysiology covers defective cobalamin absorption, transport, and cellular uptake with TCN2 as an explicit gene, decreased cobalamin transport, reduced cobalamin availability, downstream impaired active-cofactor synthesis, methylmalonic aciduria, homocystinuria, megaloblastic anemia, failure to thrive, and hydroxocobalamin therapy.

Concordance and completeness

Judgement: correct subtype mapping and high concordance.

IEMbase is more TCN2-specific for chronic diarrhea and apathy, while DisMech is stronger for umbrella mechanism and treatment rationale. DisMech also includes immunodeficiency in the TCN2 subtype description, a clinically useful detail not prominent in the IEMbase characteristic rows.

Curation actions

  • Keep the generated mapping to Inborn_Disorder_of_Cobalamin_Metabolism_and_Transport.yaml#TCN2 deficiency.
  • No separate TCN2-only file is needed unless the project later splits transport disorders out of the cobalamin umbrella.
  • Consider chronic diarrhea, apathy, and explicit cyanocobalamin treatment as optional future subtype enrichments.